Neurotoxicity Research Papers - Academia.edu (original) (raw)

Background: Rotenone, a chemical compound produced naturally by leguminous plants, has conventionally been used as a pesticide by blocking the uptake of oxygen by body cells. Our study aimed to investigate the effect of spirulina on oxidative damage, inflammation, and neurotoxicity in male mice treated by rotenone. Methods: The experimental animals were divided into 5 groups. Group (I) served as control that received Dimethyl Sulfoxide (DMSO); Group (II) mice treated with rotenone (1.5 mg/ kg, s.c.3 times per week); Group (III) mice received rotenone/L-dopa (25 mg/kg, P.O. daily); Group (IV) and Group (V) mice were treated with rotenone/spirulina (200 and 400 mg/kg, P.O. daily) respectively for two weeks. Results: Rotenone-treated mice indicated impaired motor coordination and activity in wire hanging, wood walking, open field, and stair tests. Furthermore, rotenone treatment caused elevation in striatal levels of Malondialdehyde (MDA), Nitric Oxide (NO), Tumor Necrosis Factor (TNF-α), Interleukin-1 beta (IL-1β), and caspase 3 and decrement in Bcl-2; dopamine and Glutathione (GSH) levels. Moreover, severe neuronal degeneration, striatal DNA fragmentation, and increased striatal 8-OHdG levels and MTH1 expression in the rotenone group. Additionally, spirulina treatment prevented rotenone-induced motor deficits striatal DNA fragmentation and demonstrated good restoration of the substantial neurons with reservation of the typical dark appearance. Besides, rotenone-induced biochemical changes were ameliorated by spirulina treatment as dopamine, Bcl-2, and GSH levels were increased, and striatal MDA, TNF-α, IL-1β, and caspase 3 levels were decreased. Conclusion: Natural products like spirulina could reverse rotenone-induced neurotoxicity in male mice due to their anti-inflammatory and antioxidant properties.

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- Inflammation, Oxidative Stress, Neurotoxicity, Spirulina

Although the favorable effects of physical exercise in neurorehabilitation after traumatic brain injury (TBI) are well known, detailed pathologic and functional alterations exerted by previous physical exercise on post-traumatic cerebral inflammation have been limited. In the present study, it is showed that fluid percussion brain injury (FPI) induced motor function impairment, followed by increased plasma fluorescein extravasation and cerebral—inflammation characterized by interleukin-1β, tumor necrosis factor-α (TNF-α) increase, and decreased IL-10. In addition, myeloperoxidase (MPO) increase and Na+,K+-ATPase activity inhibition after FPI suggest that the opening of blood–brain barrier (BBB) followed by neurtrophils infiltration and cerebral inflammation may contribute to the failure of selected targets leading to secondary damage. In fact, Pearson’s correlation analysis revealed strong correlation of MPO activity increase with Na+,K+-ATPase activity inhibition in sedentary rats. Statistical analysis also revealed that previous running exercise (4 weeks) protected against FPI-induced motor function impairment and fluorescein extravasation. Previous physical training also induced IL-10 increase per se and protected against cerebral IL-1β, and TNF-α increase and IL-10 decrease induced by FPI. This protocol of physical training was effective against MPO activity increase and Na+,K+-ATPase activity inhibition after FPI. The present protection correlated with MPO activity decrease suggests that the alteration of cerebral inflammatory status profile elicited by previous physical training reduces initial damage and limits long-term secondary degeneration after TBI. This prophylactic effect may facilitate functional recovery in patients suffering from brain injury induced by TBI.

- by Luiz Fernando Silva
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- Pharmacology, Animal Behavior, Traumatic Brain Injury, Toxicology

On the basis of previous work showing that flavonoids structurally related to quercetin are neuroprotective for cells in culture, this work was directed towards determining if several flavonoids (quercetin, fisetin and catechin) could acutely and by an intraperitoneal (IP) route reach significant cerebral concentrations and either prevent or facilitate recovery from a brain lesion induced by focal ischemia in rats.

- by Jessika Urbanavicius and +1
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- Image Analysis, Neurotoxicity, Clinical Sciences, Structure activity Relationship

In assessing and assimilating the neurodevelopmental basis of the so-called movement disorders it is probably useful to establish certain concepts that will modulate both the variation and selection of affliction, mechanisms-processes and diversity of disease states. Both genetic, developmental and degenerative aberrations are to be encompassed within such an approach, as well as all deviations from the necessary components of behaviour that are generally understood to incorporate "normal" functioning. In the present treatise, both conditions of hyperactivity/hypoactivity, akinesia and bradykinesia together with a constellation of other symptoms and syndromes are considered in conjunction with the neuropharmacological and brain morphological alterations that may or may not accompany them, e.g. following neonatal denervation. As a case in point, the neuroanatomical and neurochemical points of interaction in Attention Deficit and Hyperactivity disorder (ADHD) are examined with reference to both the perinatal metallic and organic environment and genetic backgrounds. The role of apoptosis, as opposed to necrosis, in cell death during brain development necessitates careful considerations of the current explosion of evidence for brain nerve growth factors, neurotrophins and cytokines, and the processes regulating their appearance, release and fate. Some of these processes may possess putative inherited characteristics, like asynuclein, others may to greater or lesser extents be endogenous or semi-endogenous (in food), like the tetrahydroisoquinolines, others exogenous until inhaled or injested through environmental accident, like heavy metals, e.g. mercury. Another central concept of neurodevelopment is cellular plasticity, thereby underlining the essential involvement of glutamate systems and Nmethyl-D-aspartate receptor configurations. Finally, an essential assimilation of brain development in disease must delineate the relative merits of inherited as opposed to environmental risks not only for the commonly-regarded movement disorders, like Parkinson's disease, Huntington's disease and epilepsy, but also for afflictions bearing strong elements of psychosocial tragedy, like ADHD, autism and Savantism.

- by Richard Kostrzewa
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- Genetics, Multiple sclerosis, Epilepsy, Brain development

A conditioned stimulus (CS) associated with a fearsome unconditioned stimulus (US) generates learned fear. Acquired fear is at the root of a variety of disorders, among which are phobias, generalized anxiety, and the posttraumatic stress disorder (PTSD). The simplest way to inhibit learned fear is to extinguish it, which is usually done by repeatedly presenting the CS alone, so that a new association, CS-"no US", will eventually overcome the previously acquired CS-US association. Extinction was first described by Pavlov as a form of "ïnternal inhibition" and was recommended by Freud and Ferenczi in the 1920s (who called it "habituation") as the treatment of choice for phobic disorders. It is used with success till this day, often in association with anxiolytic drugs. Extinction has since then been applied, also successfully and also often in association with anxiolytics, to the treatment of panic, generalized anxiety disorders and, more recently, PTSD. Extinction of learned fear involves gene expression, protein synthesis, N-methyl-D-aspartate (NMDA) receptors and signaling pathways in the hippocampus and the amygdala at the time of the first CS-no US association. It can be enhanced by increasing the exposure to the "no US" component at the time of behavioral testing, to the point of causing the complete uninstallment of the original fear response. Some theorists have recently proposed that reiteration of the CS alone may induce a reconsolidation of the learned behavior instead of its extinction. Reconsolidation would preserve the original memory from the labilization induced by its retrieval. If true, this would of course be disastrous for the psychotherapy of fear-motivated disorders. Here we show that neither the CS nor retrieval cause anything remotely like reconsolida-tion, but just extinction. In fact, our findings indicate that the reconsolidation hypothesis is essentially incorrect, at least for the form of contextual fear most commonly studied in rodents. Therefore, it seems safe to continue using extinction-based forms of therapy for anxiety disorders secondary to acquired fear. Further, it is useful and desirable to devise procedures by which the "no US" component of the extinction is strengthened in order to alleviate the symptoms of victims of acquired fear.

- by Monica Vianna
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- Fear, Enzyme Inhibitors, Gene expression, Protein synthesis

Valeriana officinalis have been used in traditional medicine for its sedative, hypnotic, and anticonvulsant effects. There are several eports in the literature supporting a GABAergic mechanism of action for valerian. The rationale of the present work is based on the concept that by decreasing neuronal network excitability valerian consumption may contribute to neuroprotection. The aim of our investigation was to evaluate the neuroprotective effects ofV. officinalis against the toxicity induced by amyloid beta peptide 25–35 [Aβ(25–35)]. Cultured rat hip-pocampal neurons were exposed to Aβ(25–35)(25 μM) for 24–48 h,after which morphological and biochemical properties were evaluated. The neuronal injury evoked by Aβ, which includes a decrease in cell educing capacity and associated neuronal degeneration, was prevented by valerian extract. Analysis of intracellular free calcium ([Ca2+]i)indicated that the neuroprotective mechanisms may involve the inhibition of excess influx of Ca2+ following neuronal injury. Moreover, membrane peroxidation in rat hippocampal synaptosomes was evaluated, and our data indicate that valerian extract partially inhibited ascorbate/iron-induced peroxidation. In conclusion we show evidence that the signalling pathways involving [Ca2+]i and the redox state of the cells may play a central ole in the neuroprotective properties ofV. officinalis extract against Aβ toxicity. The novelty of the findings of the present work, indicating neuroprotective properties of valerian against Aβ toxicity may, at the long-term, contribute to introduction of a new elevant use of valerian alcoholic extract to prevent neuronal degeneration in aging or neurodegenerative disorders.

- by Sandra Santos
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- Traditional Medicine, Cell Culture, Hippocampus, Neuronal Network

One hotly debated topic within the field of intimate partner violence is the degree to which IPV can be understood as primarily a uni-directional versus bi-directional phenomena; this topic forms a key component of the gender symmetry... more

- by Farel Ikhsan
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- Neuroscience, Immunology, Autism, Multiple sclerosis

The endogenous cannabinoid system is a new signaling system composed by the central (CB1) and the peripheral (CB2) receptors, and several lipid transmitters including anandamide and 2-arachidonylg-lycerol. This system is the target of natural cannabinoids, the psychoactive constituents ofCannabis sativa preparations (marijuana, hashish). Acute and chronic cannabis exposure has been associated with subjective feelings of pleasure and relaxation, but also to the onset of psychiatric syndromes, a decrease of the efficacy of neuroleptics and alterations in the extrapyramidal system regulation of motor activity. These actions points to a tight association of the cannabinoid system with the brain dopaminergic circuits involved in addiction, the clinical manifestation of positive symptoms of schizophrenia and Parkinson’s disease. The present work discuss anatomical, biochemical and pharmacological evidences supporting a role for the endogenous cannabinoid system in the modulation of dopaminergic transmission. Cannabinoid CB1 receptors are present in dopamine projecting brain areas. In primates and certain rat strains it is also located in dopamine cells of the A8, A9 and A10 mesencephalic cell groups, as well as in hypothalamic dopaminergic neurons controlling prolactin secretion. CB1 receptors co-localize with dopamine D1/D2 receptors in dopamine projecting fields. Manipulation of dopaminergic transmission is able of altere the synthesis and release of anandamide as well as the expression of CB1 receptors. Additionally, CB1receptors can switch its transduction mechanism to oppose to the ongoing dopamine signaling. Acute blockade of CB1 receptor potentiates the facilitatory role of dopamine D2 receptor agonists on movement. CB1 stimulation results in sensitization to the motor effects of indirect dopaminergic agonists. The dynamics of these changes indicate that the cannabinoid system is an activity-dependent modulator of dopaminergic transmission, an hypothesis relevant for the design of new therapeutic strategies for dopamine-related diseases such as the psychosis and Parkinson’s disease.

- by Daniele Piomelli
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- Dopamine, Prolactin, Vitamin D receptor, Neurotoxicity

Concerns related to higher levels of acrylamide in processed carbohydrate-rich foods, especially in fried potato products, are well known. This article provides updates on various aspects of acrylamide in processed potato products including mechanisms of acrylamide formation and health risks due to its intake. Levels of reducing sugars in potatoes are considered as a main factor contributing towards the formation of acrylamide in processed potato products. Useful approaches in lowering the levels of reducing sugars such as use of suitable varieties, storage methods, storage temperature and duration of storage are described and discussed. Importance and practical utility of various steps before and during the processing that can contribute in reducing the final concentration of acrylamide are highlighted. Progress made and present status of potato processing industry in India are part of this article. The article describes varietal improvement and spread of short-term and long-term storage technologies in India and their contribution towards round the year availability of processing grade potatoes to the processing industries and how all this has helped in achieving reduced levels of acry-lamide in chips and French fries. Outcome and implications of cold-induced sweetening tolerance in potatoes are presented along with other management practices and strategies that can lower the acrylamide levels in processed potato products. Future lines of work have been suggested to make the consumption of fried potato products safer.

- by Vijay Paul and +1
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- Atherosclerosis, Potato, Neurotoxicity, Human health

Neurochemistry and drug addiction. Neurocognitive approach. Cognitive Neuroscience. Research for the Postgraduate Program in Cognitive Sciences of the University of Costa Rica. This research establishes a theoretical basis for the biochemical and neurophysiological bases of behavior and mental phenomena, as well as analyzing the neuropathologies derived from the consumption of toxic substances. Plausible explanations are given for the relationships between toxic and addictive and addictive behaviors, and their neurophysiological and genetic bases. // Neuroquímica y toxicodependencia. Enfoque de neurocognoscitivo. Neurociencias Cognoscitivas. Investigación para el Programa de Postgrado en Ciencias Cognoscitivas de la Universidad de Costa Rica. Esta investigación, establece una fundamenta teórica de las bases bioquímicas y neurofisiológicas de la conducta y de los fenómenos mentales, así como analiza las neuropatologías derivadas del consumo de tóxicos. Se plantean explicaciones plausibles de las relaciones entre tóxicos y conductas dependientes y adictivas, y sus bases neurofisiológicas y genéticas. // Rodolfo J. Rodríguez-Rodríguez. E-Mail: rodolfojrr@gmx.com

The pineal product melatonin has remarkable antioxidant properties. It is secreted during darkness and plays a key role in various physiological responses including regulation of circadian rhythms, sleep homeostasis, retinal... more

- by Seithikurippu Pandi-perumal and +1
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- Free Radicals, Aging, Oxidative Stress, Mitochondria

Since its introduction in the late 1970s for the treatment of strabismus and blepharospasm, botulinum toxin (BoNT) has been increasingly used in the interventional treatment of several other disorders characterized by excessive or inappropriate muscle contractions. Over the years, the number of primary clinical publications has grown exponentially, and still continues to increase. It has been shown that BoNT blocks cholinergic nerve endings in the autonomic nervous system but does not block nonadrenergic non-cholinergic responses mediated by nitric oxide (NO).

- by G. Brisinda
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- Autonomic Nervous System, Clinical Practice, Neurotoxicity, Clinical Sciences

Highest rates of snake envenoming and mortalities in South Asia, Southeast Asia, Sub-Share Africa with India reporting the most deaths. World Health Organization listed snakebite as a neglected disease. Clinical manifestations of snakebite include overwhelming fear, nausea vomiting diarrhea, vertigo, fainting, tachycardia, and cold, clammy skin. Most snakes cause neurotoxicity. Paresthesia throughout the body, as well as difficulty in speaking and breathing. Several other neurological features have been reported after snake envenomation which is likely to be direct neurotoxic effects. Mechanisms of many these acute manifestations are not clear. Myokymia has been reported mainly from United States following rattlesnake (Crotalusspp). Altered consciousness and deep comma has been reported in 64 % of patient after common krait envenomation. Delayed neurotoxicity also been reported. Anti-venom treatment should be given as soon possible, low dose anti-snake venom (ASV) is not inferior to high dose ASV. Improvement in neurotoxicity has been reported when anti-venom had been administered early. Prevention by avoiding areas heavily infested with snakes. Bite from a dead snake often contains large amount of venom. There is an urgent need for better treatment in neurotoxic envenoming.

- by Firdaus Hayati
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- Snake venoms, Snakebite, Neurotoxicity, Snakes

In the recent past, India has made substantial progress not only in production and productivity of potatoes but also in utilizing potatoes for processed products mainly chips and French fries. This quantitative improvement now demands for enhancement of qualitative aspects of processed potato products. Among the various issues that are associated with quality aspects, one of the important issues is the levels of acrylamide in different processed potato products. This article brings about various aspects which are directly or indirectly linked with the levels of acrylamide in processed potato products. Besides covering the concerns and various health issues related to acrylamide in our diet, the article suggests guidelines that can assist in achieving an overall reduction in the levels of acrylamide in processed potato products. Both, organized as well as unorganized sectors involved in the potato processing will be benefited from the guidelines presented here. These guidelines along with the outcome from the suggested lines of future research work will be of help in further improving the qualitative aspects. All these efforts will allow India to compete globally in terms of quality and safety aspects of different processed potato products. The information presented here will be of relevance and practical use not only to processors and potato based processing industries but also to potato growers, cold store owners and consumers as well.

- by Rajarathnam Ezekiel and +1
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- Potato, Neurotoxicity, Maillard reaction, French Fries

In the last decade, a large number of studies using D D 9 -tetrahydrocannabinol (THC), the main active principle derivative of the marijuana plant, or cannabinoid synthetic derivatives have substantially contributed to advance in the... more

- by Tomas Palomo
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- Multiple sclerosis, Chronic Pain, Movement disorders, Brain

- by Mark Bonta and +1
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- Ethnobotany, Neurotoxicity, Cycads, Dioon

Neurotoxins represent unique chemical tools, providing a means to 1) gain insight into cellular mechanisms of apopotosis and necrosis, 2) achieve a morphological template for studies otherwise unattainable, 3) specifically produce a singular phenotype of denervation, and 4) provide the starting point to delve into processes and mechanisms of nerve regeneration and sprouting. There are many other notable uses of neurotoxins in neuroscience research, and ever more being discovered each year. The objective of this review paper is to highlight the broad areas of neuroscience in which neurotoxins and neurotoxicity mechanism come into play. This shifts the focus away from neurotoxins per se, and onto the major problems under study today. Neurotoxins broadly defined are used to explore neurodegenerative disorders, psychiatric disorders and substance use disorders. Neurotoxic mechanisms relating to protein aggregates are indigenous to Alzheimer disease, Parkinson's disease. NeuroAIDS is a disorder in which microglia and macrophages have enormous import. The gap between the immune system and nervous system has been bridged, as neuroinflammation is now considered to be part of the neurodegenerative process. Related mechanisms now arise in the process of neurogenesis. Accordingly, the entire spectrum of neuroscience is within the purview of neurotoxins and neurotoxicity mechanisms. Highlights on discoveries in the areas noted, and on selective neurotoxins, are included, mainly from the past 2 to 3 years. FP Graham Publishing Co., www.NeurotoxicityResearch.com damage and chromosomal aberrations in cultured Chinese hamster lung fibroblast cells. Mutat. Res. 474, 25-33. Kadiu I, JG Glanzer, J Kipnis, HE Gendelman and MP Thomas (2005) Mononuclear phagocytes in the pathogenesis of neurodegenerative diseases. Neurotox. Res. 8, 25-50. Kalivas PW, KK Szumlinski and P Worley (2004) Homer2 gene deletion in mice produces a phenotype similar to chronic cocaine treated rats. Neurotox. Res. 6, 385-387. Kaul M and SA Lipton (2005) Experimental and potential future therapeutic approaches for HIV-1 associated dementia targeting receptors for chemokines, glutamate and erythropoietin. Neurotox. Res. 8, 167-186. Kawashima H, Y Iida, Y Kitamura and H Saji (2004) Binding of 4-(4-chlorophenyl)-1-[4-(4-fluorophenyl)-4-oxobutyl]pyridinium ion (HPP + ), a metabolite of haloperidol, to synthetic melanin: implications for the dopaminergic neurotoxicity of HPP + . Neurotox. Res. 6, 535-542. Kheradpezhouh M, S Shavali and M Ebadi (2003) Salsolinol causing parkinsonism activates endoplasmic reticulum-stress signaling pathways in human dopaminergic SK-N-SH cells. Neurosignals 12, 315-324. Kim WK, X Avarez and K Williams (2005) The role of monocytes and perivascular macrophages in HIV and SIV neuropathogenesis: information from non-human primate models. Neurotox. Res. 8, 107-115. Kinney GG, M Burno, UC Campbell, LM Hernandez, D Rodriguez, LJ Bristow and PJ Conn (2003) Metabotropic glutamate subtype 5 receptors (mGluR5) modulate locomotor activity and sensorimotor gating in rodents. J. Pharm. Exp. Ther. 306, 116-123. Kiss P, A Tamas, A Lubics, M Szalai, L Szalontay, I Lengvari and D Reglodi (2005) Development of neurological reflexes and motor coordination in rats neonatally treated with monosodium glutamate. Neurotox. Res. 8, 235-244. Kemmmerling U, P Muñoz, MA Carrasco and C Hidalgo (2005) Redox activation of ryanodine receptors induces calcium signals and CREB AND ERK phosphorylation in hippocampal and N2a neurons. Neurotox. Res. 8, 336. Klawitter V, P Morales, P Huaiquín, D Bustamante and M Herrera-Marschitz (2005) Effects of perinatal asphyxia on cell survival, neuronal phenotype and neurite growth evaluated with organotypic triple cultures. Neurotox. Res. 8, 334. Klein DF and J Stewart (2004) Genes and environment: nosology and psychiatry. Neurotox. Res. 6, 11-16. Klivenyi P, D Siwek, G Gardian, L Yang, A Starkov, C Cleren, RJ Ferrante, NW Kowall, A Abeliovich and MF Beal (2006) Mice lacking α-synuclein are resistant to mitochondrial toxins. Neurobiol. Dis. 21, 541-548. Kostrzewa RM (1995) Dopamine receptor supersensitivity. Neurosci. Biobehav. Rev. 19, 1-17. Kostrzewa RM, JP Kostrzewa and R Brus (2003) Dopamine receptor supersensitivity: an outcome and index of neurotoxicity. Neurotox. Res. 5, 111-118. Kostrzewa RM, JP Kostrzewa, P Nowak, RA Kostrzewa and R Brus (2004) Dopamine D 2 agonist priming in intact and dopaminelesioned rats. Neurotox. Res. 6, 457-462. Kostrzewa JP and RM Kostrzewa (2005) p-Chloroamphetamine enhances dopamine release (striatal in vivo microdialysates) after 5-HT lesion of Parkinsonian rats. Neurotox. Res. 8, 321. Kostrzewa RM, JP Kostrzewa and R Brus (2005) Serotonin systems mediate and modulate dopamine in a Parkinsonian rodent model.

- by Richard Kostrzewa
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- Neurotoxicity, Protein Aggregation, Neurotoxins, Nerve Regeneration
- by Richard Kostrzewa
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- Free Radicals, Apoptosis, Cell Culture, Neuroprotection

os capítulos que incluye el libro electrónico Temas selecci0
nados de toxinas con implicaciones biomédicas y métodos
para su estudioresultan de una primera aproximación para
mostrar de manera panorámica el trabajo de investigación que
desarrollan los miembros de la Red Iberoamericana Temática
CYTED 212RT0467 (Biotox) en el campo de las toxinas con implicaciones
para la Biomedicina.
El texto no pretende ser exhaustivo, más bien se trata de
un material introductorio, de carácter general, cuyo propósito
comunicativo es servir como presentación delas líneas de investigación
de los principales grupos de Argentina, Brasil, Chile,
Costa Rica, Cuba, España, México y Venezuela pertenecientes a
la Red Biotox que se ocupan de toxinas o cuentan con un arsenal
metodológico para su caracterización físico-química,
biológica o su acción farmacológica.
Los autores son reconocidos especialistas en sus respectivas
áreas de trabajo a los cuales agradezco el esfuerzo en la elaboración
de este material que puede ser útil a profesionales y
estudiantes interesados en conocer aspectos del estado del arte
en investigaciones sobre toxinas o métodos para su estudio,
en el ámbito iberoamericano. En principio, estos textos fueron
concebidos para apoyar las exposiciones que se realizaron en
el I Taller-Científico Técnico de Biotox celebrado en el Instituto
Clodomiro Picado, Costa Rica (6-10 agosto, 2012), que dio inicio a
las actividades de la Red. Invito a los interesados a acompañar
la lectura de los artículos con las correspondientes presentaciones
de sus autores. Las presentaciones pueden encontrarse
en la Multimedia: Memorias de las actividades de la Red CYTED
212RT0467, Biotox: Toxinas de Interés para la Biomedicina, 2012
(Costa Rica) y posteriormente serán depositadas en la página
Web de la Red que se encuentra en desarrollo

- by Enrique Soto
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- Toxicology, Neurotoxicity

Dichlorvos is an organophosphate insecticide effectively used
against mushroom flies, aphids, spiders, mites, caterpillars and
thrips. Toxicity of dichlorvos is confirmed by air, water and food
via inhalation, dermal, absorption and ingestion. Earlier studies
velate the dichlorvos administration with the toxicity of the
reproductive system, respiratory system, cardiovascular system
and nervous system. Primarily, it affects the nervous system
through cholinesterase inhibition or anticholinesterase effect and
also leads to increased intracellular calcium level, oxidative stress
and the rate of lipid peroxidation in the brain mitochondria.
Mitochondria are pleomorphic organelles that generate the ATP
supply for the cells. Disturbance in the electron transport chain
(ETC) of mitochondria by the dichlorvos ultimately increases the
ROS production, thereby leading to an increase of oxygen
consumption and decrease of ATP synthesis which is the hallmark
of the neuronal lesions. The increased calcium level is reported to
be associated with neurodegenerative diseases such as
Alzheimer’s disease, Parkinson’s disease and amyotrophic lateral
sclerosis. Since, the brain is a controlling and coordinating organ
in the body, therefore toxic effects of dichlorvos on it will also be
deleterious to other organ-systems indirectly. Current review deals
with possible implications of impairment of cholinergic circuit and
brain mitochondrial functions carried by dichlorvos which may be
the cause of potential neurotoxicity.

Botulinum neurotoxin (BoNT), for more than a hundred years, has been a recognized poisonous principle in spoiled food. As its chemical structure became unraveled, and as more knowledge was gained over its mechanism of toxicity, it became clear that BoNT had the potential to act therapeutically as a targeted toxin that could inactivate specific nerve populations, and thus achieve a therapeutic goal. BoNT has evolved over the past 25 years into a viable therapeutic, now being a first line treatment for dystonia, overtly altering the course of progression of this disorder. BoNT is used for hyperhidrosis and gustatory sweating syndrome, alleviation of pain, as a treatment for overactive bladder, achalasia and anal fissure; and it has gained popularity as a cosmetic aid. Many other possible uses are being explored. The greatest potential for BoNT may lie in its being a molecular Trojan Horse -able to carry a specific enzyme or specific drug to the inside of a cancer or other type of cell while bypassing other cells and thereby having little or no ill effect. BoNT's pharmaceutical potential is boundless.

- by Richard Kostrzewa
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- Research, Pharmaceutical, Neurotoxicity, Clinical Sciences

The neurodegenerative and neurotoxic aspects of schizophrenia and/or psychosis involve genetic, epigenetic, and neurotoxic propensities that impinge upon both the symptom domains and the biomarkers of the disorder, involving cellular apoptosis/excitotoxicity, increased reactive oxygen species formation, viral and bacterial infections, anoxic birth injury, maternal starvation, drugs of abuse, particularly cannabis, metabolic accidents, and other chemical agents that disrupt normal brain development or the integrity of brain tissues. Evidence for premorbid and prodromal psychotic phases, aspects of neuroimaging, dopamine, and psychosis vulnerability, and perinatal aspects provide substance for neurodegenerative influences. Not least, the agencies of antipsychotic contribute to the destructive spiral that disrupts normal structure and function. The etiopathogenesis of psychosis is distinguished also by disruptions of the normal functioning of the neurotrophins, in particular brain-derived neurotrophic factor, dyskinesic aspects, immune system disturbances, and metabolic aspects. Whether detrimental to neurodevelopment or tissue-destructive, or an acceleration of neurotoxic pathways, the notion of neurodegeneration in the pathophysiology of schizophrenia spectrum and psychotic disorders continues to gather momentum.

- by Danilo Garcia
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- Neurodegenerative Diseases, Brain, Neurotoxicity, Clinical Sciences

There is clinical and experimental evidence indicating that neurocircuitries of the hippocampus are vulnerable to hypoxia/ischemia occurring at birth, inducing, upon re-oxygenation/re-circulation, delayed neuronal death, but also compensatory mechanisms, including neurogenesis. In the present report, perinatal asphyxia was induced by immersing foetuses-containing uterine horns removed from ready-to-deliver rats into a water bath at 37°C for 20 min. Some pups were delivered immediately after the hysterectomy to be used as non-asphyxiated caesarean-delivered controls. The pups were sacrificed after seven days for preparing organotypic hippocampal cultures. The cultures were grown on a coverslip in a medium-containing culture tube inserted in a hole of a roller device standing on the internal area of a cell incubator at 35°C, 10% CO2. At daysin vitro (DIV) 25–27, cultures were fixed for assaying cell proliferation and neuronal phenotype with antibodies against 5-bromo-2 deoxyuridine (BrdU) and microtubule associated protein-2 (MAP-2), respectively. Confocal microscopy revealed that there was a 2-fold increase of BrdU-positive, but a 40% decrease of MAP-2-positive cells/mm3 in cultures from asphyxiaexposed, compared to that from control animals. Approximately 30% of BrdU-positive cells were also positive for MAP-2 (approximately 4800 cells), mainly seen in the dentate gyrus of the hippocampus, demonstrating a 3-fold increase of postnatal neurogenesis, when the total amount of double-labelled cells seen in cultures from asphyxia-exposed animals is compared to that from control animals.

- by Paola Morales
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- Confocal Microscopy, Hippocampus, Neurotoxicity, Neurons

Alzheimer's disease (AD) and Parkinson's disease (PD) are the most common causes of dementia and movement disorders in the elderly. While progressive accumulation of oligomeric amyloid-b protein (Ab) has been identified as one of the central toxic events in AD leading to synaptic dysfunction, accumulation of a-synuclein (a-syn) resulting in the formation of oligomers has been linked to PD. Most of the studies in AD have been focused on investigating the role of Ab and Tau; however, recent studies suggest that a-syn might also play a role in the pathogenesis of AD. For example, fragments of a-syn can associate with amyloid plaques and Ab promotes the aggregation of a-syn in vivo and worsens the deficits in a-syn tg mice. Moreover, a-syn has also been shown to accumulate in limbic regions in AD, Down's syndrome, and familial AD cases. Ab and a-syn might directly interact under pathological conditions leading to the formation of toxic oligomers and nanopores that increase intracellular calcium. The interactions between Ab and a-syn might also result in oxidative stress, lysosomal leakage, and mitochondrial dysfunction. Thus, better understanding the steps involved in the process of Ab and a-syn aggregation is important in order to develop intervention strategies that might prevent or reverse the accumulation of toxic proteins in AD.

- by Igor Tsigelny
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- Oxidative Stress, Mice, Neurotoxicity, Clinical Sciences

Mercury is one of the most toxic substances known to humans. It has been introduced into the human environment and has also been widely used in medicine. Since circumstantial evidence exists that the pathology of Alzheimer's disease (AD) might be in part caused or exacerbated by inorganic mercury, we conducted a systematic review using a comprehensive search strategy. Studies were screened according to a pre-defined protocol. Two reviewers extracted relevant data independent of each other. One thousand and forty one references were scrutinized, and 106 studies fulfilled the inclusion criteria. Most studies were case control or comparative cohort studies. Thirty-two studies, out of 40 testing memory in individuals exposed to inorganic mercury, found significant memory deficits. Some autopsy studies found increased mercury levels in brain tissues of AD patients. Measurements of mercury levels in blood, urine, hair, nails, and cerebrospinal fluid were inconsistent. In vitro models showed that inorganic mercury reproduces all pathological changes seen in AD, and in animal models inorganic mercury produced changes that are similar to those seen in AD. Its high affinity for selenium and selenoproteins suggests that inorganic mercury may promote neurodegenerative disorders via disruption of redox regulation. Inorganic mercury may play a role as a co-factor in the development of AD. It may also increase the pathological influence of other metals. Our mechanistic model describes potential causal pathways. As the single most effective public health primary preventive measure, industrial, and medical usage of mercury should be eliminated as soon as possible.

- by Harald Walach
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- Alzheimer's Disease, Selenium, Neurotoxicity, Systematic review
- by Enrique Soto
- •
- Neuroscience, Physiology, Biophysics, Research Methodology

We characterized undifferentiated (UN) and three differentiation conditions of the SH-SY5Y neuroblastoma cell line for phenotypic markers of dopaminergic cells, sensitivity to the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridinium ion (MPP), the requirement to utilize the dopamine (DA) transporter (DAT) for MPP toxicity, and the neuroprotective effects of pramipexole. Cells were differentiated with retinoic acid (RA), 12-O-tetradecanoly-phorbol-13-acetate (TPA), and RA followed by TPA (RA/TPA). RA/TPA treated cells exhibited the highest levels of tyrosine hydroxylase and DAT but lower levels of vesicular monoamine transporter. The kinetics of [3H]DA uptake and [3H]MPP uptake to DAT in RA/TPA differentiated cells were similar to that of rat and mouse caudate-putamen synaptosomes. RA/TPA differentiated cells evidenced high sensitivity to the neurotoxic effects of MPP (0.03 to 3.0 mM), and the neurotoxic effects of MPP were blocked with the DAT inhibitor 1-(2-[bis(4-fluorophenyl)methoxy]ethyl)-4-(3-phenylpropyl)piperazine (GBR 12909). DA-induced cell death was not more sensitive in RA vs RA/TPA differentiated cells and was not inhibited by transporter inhibitors. RA/TPA differentiated cells exhibited 3- fold and 6-fold higher levels, respectively, of DA D2 and D3 receptors than UN or RA differentiated cells. Pretreatment with pramipexole was protective against MPP in the RA/TPA differentiated cells but not in undifferentiated or RA differentiated cells. The neuroprotective effect of pramipexole was concentration-dependent and dopamine D2/D3 receptor dependent. In contrast, protection by pramipexole against DA was not DA receptor dependent. Further characterization of the neuroprotective effects of DA agonists in this model system can provide unique information about DA receptor dependent and independent mechanisms of neuroprotection.

- by Ahmed Gbr
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- Kinetics, Dopamine, Cell line, Cell Differentiation

Ocimum gratissimum is an herbaceous perennial shrub which is widely distributed in many regions.
It is consumed in food as seasoning locally in Nigeria. In the present study, the effect of the acute
administration of the aqueous leaf extract of Ocimum gratissimum (AeOG) on prefrontal cortical
neurons was checked to assess its neurotoxicity potential. Thirty adult male Wistar rats weighing
between 190-210 g were divided into 5 groups (n=6). Group A (control) received 1 ml of normal
saline (p.o), groups B-E received 100, 200, 300 and 400 mg/kg AeOG (p.o) respectively. Treatment
lasted for fourteen days. Twenty-four hours after treatment, animals were sacrificed and their
brains were removed. The prefrontal cortices neuronal morphology was studied using haematoxylin
and eosin (H&E) stain; while activities of acid phosphatase (ACP) and alkaline phosphatase (ALP)
were assayed in the cerebral homogenate. AeOG administration at doses 300 and 400 mg/kg
cause neuronal fragmentation and central chromatolysis with significant (P<0.05) increases in the
activities of cerebral ACP and ALP. Our findings show that the acute use of AeOG caused neuronal
fragmentation and central chromatolysis which are response to axonal injuries and may leads to
onset of neurodegenerative diseases and affect cognitive and executive functions of the prefrontal
cortex.
Key words: Ocimum gratissimum, Acid Phosphatase (ACP), Alkaline Phosphatase (ALP), Neurogenerative diseases, Rat.

- by Imam Aminu
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- Neurotoxicity

Symptoms of schizophrenia are improved by dopamine antagonists and exacerbated by dopamine-releasing agents, suggesting hyperactivity of dopamine. However, chronic blockade of glutamate neurotransmission by antagonists at the Nmethyl-D-aspartate (NMDA) receptor subtype produces a pathophysiological state resembling schizophrenia. A link between cortical glutamate/NMDA deficiency and subcortical dopamine hyperactivity, particularly in the mesolimbic pathway, has been hypothesized in schizophrenia. Here we show that hyperactivity produced by NMDA receptor blockade is dependent upon stimulation of the dopamine D 3 receptor subtype. Since D 3 receptor antagonists and antipsychotics produced very similar effects, our results add to the growing evidence suggesting that D 3 receptor blockade might produce antipsychotic effects.

- by Jorge Diaz
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- Schizophrenia, Dopamine, Neurotoxicity, Clinical Sciences

The intramuscular application of botulinum toxin type A (BoNT/A) has emerged to be an established treatment option to reduce muscular hyperactivity due to spasticity in children with cerebral palsy. Accurate injection is a prerequisite for efficient and safe treatment with BoNT/A. So far, treatment procedures have not been standardized. This paper is a short review of different injection techniques, i.e., manual needle placement as well as guidance by electromyography, electrical stimulation, and ultrasound. Advantages and disadvantages of the different injection techniques are discussed with a focus on needle positioning within the targeted muscle, injection close to the neuromuscular junction and diffusion of BoNT/A within the target muscles and through fascia. The additional information gained by each injection technique is weighed in terms of the clinical impact for children with cerebral palsy.

- by Florian Heinen
- •
- Ultrasound, Cerebral Palsy, Child, Diffusion

The levels of the essential pyridine nucleotide, NAD + and its reduced form NADH have not been documented in MS patients. We aimed to investigate NAD + and NADH levels in serum in patients with different disease stages and forms of MS. NAD + and NADH levels were measured in the serum from 209 patients with relapsing remitting MS (RRMS), 136 with secondary progressive MS (SPMS), 51 with primary progressive MS (PPMS), and 99 healthy controls. All patients were in a clinically stable phase. Serum NAD + levels declined by at least 50% in patients with MS compared to controls (17.9±3.2 μg/ml; p=0.0012). Within the MS sub-groups NAD + levels were higher in RRMS (9.9±2.9 μg/ml; p=0.001) compared to PPMS (6.3±2.1 μg/ml; p=0.003) and SPMS (7.8±2.0 μg/ml; p=0.005). A two-fold increase in NADH levels (p=0.002) and at least three-fold reduction in the NAD + /NADH ratio (p=0.009) were observed in MS patients compared to controls. Serum NAD + and NADH levels are may be associated with disease progression in MS. Given the importance of NAD + in the maintenance of normal cellular function, it is likely that this molecule is of therapeutic relevance in MS.

- by Sarah Coggan and +1
- •
- Inflammation, Immunohistochemistry, Signal Transduction, Amyotrophic Lateral Sclerosis
- by Sergio Cárdenas
- •
- Cell line, Neurotoxicity, Substantia nigra, Clinical Sciences

Data accumulated through the past 15 years showed that memory consolidation of one-trial avoidance learning relies on a sequence of molecular events in the CA1 region of the hippocampus that is practically identical to that of long-term potentiation (LTP) in that area. Recent findings have indeed described CA1 LTP concomitant to the consolidation of this and other tasks. However, abundant evidence suggests that, in addition, other molecular events, involving some of the same steps but with different timing and in different sequence in the basolateral amygdala, entorhinal, parietal and cingulate cortex are as important as those of the hippocampus for memory consolidation. Here we review the hippocampal mechanisms involved and the possible interconnections between all these processes. Overall, the findings indicate that memory consolidation of even a task as deceivingly simple as one-trial avoidance relies on hippocampal LTP but also requires the concomitant participation of other brain systems and molecular events. Further, they point to the mechanisms that account for the enhanced consolidation usually seen for emotionladen memories.

- by Jorge Medina
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- Long Term Potentiation, Signal Transduction, Emotions, Memory Consolidation

The Asian genus Boiga (Colubridae) is among the better studied non-front-fanged snake lineages, because their bites have minor, but noticeable, effects on humans. Furthermore, B. irregularis has gained worldwide notoriety for successfully invading Guam and other nearby islands with drastic impacts on the local bird populations. One of the factors thought to allow B. irregularis to become such a noxious pest is irditoxin, a dimeric neurotoxin composed of two three-finger toxins (3FTx) joined by a covalent bond between two newly evolved cysteines. Irditoxin is highly toxic to diapsid (birds and reptiles) prey, but roughly 1000 × less potent to synapsids (mammals). Venom plays an important role in the ecology of all species of Boiga, but it remains unknown if any species besides B. irregularis produce irditoxin-like dimeric toxins. In this study, we use transcriptomic analyses of venom glands from five species [B. cynodon, B. dendrophila dendrophila, B. d. gemmicincta, B. irregularis (Brisbane population), B. irregularis (Sulawesi population), B. nigriceps, B. trigonata] and proteomic analyses of B. d. dendrophila and a representative of the sister genus Toxicodryas blandingii to investigate the evolutionary history of 3FTx within Boiga and its close relative. We found that 92.5% of Boiga 3FTx belong to a single clade which we refer to as denmotoxin-like because of the close relation between these toxins and the monomeric denmotoxin according to phy-logenetic, sequence clustering, and protein similarity network analyses. We show for the first time that species beyond B. irregularis secrete 3FTx with additional cysteines in the same position as both the A and B subunits of irditoxin. Transcripts with the characteristic mutations are found in B. d. dendrophila, B. d. gemmicincta, B. irregularis (Brisbane population), B. irregularis (Sulawesi population), and B. nigriceps. These results are confirmed by proteomic analyses that show direct evidence of dimerization within the venom of B. d. dendrophila, but not T. blandingii. Our results also suggest the possibility of novel dimeric toxins in other genera such as Telescopus and Trimorphodon. All together, this suggests that the origin of these peculiar 3FTx is far earlier than was appreciated and their evolutionary history has been complex.

- by Bryan G Fry
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- Invasive species ecology, Invasive Species, Snake venoms, Animal venoms and toxins

Neuroprotective and neurotoxic effects of lithium: the role of different brain structures 1. Uniwersytet Jagielloński, Collegium Medicum, Koło Naukowe Chorób Afektywnych 2. Uniwersytet Jagielloński, Collegium Medicum, Koło Naukowe Psychiatrii Dorosłych 3. Uniwersytet Jagielloński, Collegium Medicum, Katedra Psychiatrii, Zakład Zaburzeń Afektywnych

- by Adrian A Chrobak and +1
- •
- Lithium, Neurodegeneration, Neuroprotection, Cerebellum

Psychiatric disorders may co-occur in the same individual. These include, for example, substance abuse or obsessive-compulsive disorder with schizophrenia, and movement disorders or epilepsy with affective dysfunctional states. Medications may produce iatrogenic effects, for example cognitive impairments that co-occur with the residual symptoms of the primary disorder being treated. The observation of comorbid disorders in some cases may reflect diagnostic overlap. Impulsivity, impulsiveness or impulsive behaviour is implicated in a range of diagnostic conditions including substance abuse, affective disorder and obsessive-compulsive disorder. These observations suggest a need to re-evaluate established diagnostic criteria and disorder definitions, focusing instead on symptoms and symptom-profiles.

- by Richard Kostrzewa
- •
- Personality, Schizophrenia, Treatment, Comorbidity

In multicellular organisms, all the cells are genetically identical but turn genes on or off at the right time to promote differentiation into specific cell types. The regulation of higher-order chromatin structure is essential for genome-wide reprogramming and for tissue-specific patterns of gene expression. The complexity of the genome is regulated by epigenetic mechanisms, which act at the level of DNA, histones, and nucleosomes. Epigenetic machinery is involved in many biological processes, including genomic imprinting, X-chromosome inactivation, heterochromatin formation, and transcriptional regulation, as well as DNA damage repair. In this review, we summarize the recent understanding of DNA methylation, cytosine derivatives, active and passive demethylation pathways as well as histone variants. DNA methylation is one of the well-characterized epigenetic signaling tools. Cytosine methylation of promoter regions usually represses transcription but methylation in the gene body m...

- by Richard Kostrzewa
- •
- DNA methylation, Neurotoxicity, Clinical Sciences, Histones

To study the influence of the central noradrenergic system on antinociceptive effects mediated by the CB 1 -receptor agonist methanandamide, intact rats were contrasted with rats in which noradrenergic nerves were largely destroyed shortly after birth with the neurotoxin DSP-4 [N-(-2-chloroethyl)-N-ethyl-2-bromobenzylamine (50 mg/kg sc 9 2, P1 and P3); zimelidine (10 mg/kg sc, 30 min pretreatment, selective serotonin reuptake inhibitor). When rats attained 10 weeks of age, monoamine and their metabolite concentrations were determined in the frontal cortex, thalamus, and spinal cord by an HPLC/ED method. Antinociceptive effects after methanandamide (10 mg/kg ip) apply were evaluated by a battery of tests. In addition, immunohistochemistry and densitometric analysis of the cannabinoid CB 1 receptor in the rat brain was performed. DSP-4 lesioning was associated with a reduction in norepinephrine content of the frontal cortex ([90 %) and spinal cord ([80 %) with no changes in the thalamus. Neonatal DSP-4 treatment produced a significant reduction in the antinociceptive effect of methanandamide in the tail-immersion test, hot-plate test and writhing tests. In the paw pressure and formalin hind paw tests results were ambiguous. These findings indicate that the noradrenergic system exerts a prominent influence on analgesia acting via the cannabinoid system in brain, without directly altering CB 1 receptor density in the brain.

- by Katarzyna Kuter and +1
- •
- Treatment Outcome, Brain, Neurotoxicity, Neurotoxins

The high rates of co-morbidity of drug addiction with depression may be attributable to shared neurobiology. Here, we discuss shared neurobiological substrates in drug withdrawal and depression, with an emphasis on changes in brain reward circuitry that may underlie anhedonia, a core symptom of depression and drug withdrawal. We explored experimentally whether clinical antidepressant medications or other treatments would reverse the anhedonia observed in rats undergoing spontaneous nicotine or amphetamine withdrawal, defined operationally as elevated brain reward thresholds. The co-administration of selective serotonin reuptake inhibitors with a serotonin-1A receptor antagonist, or the tricyclic antidepressant desipramine, or the atypical antidepressant bupropion ameliorated nicotine or amphetamine withdrawal in rats. Thus, increases in monoaminergic neurotransmission, or neuroadaptations induced by increased monoaminergic neurotransmission, ameliorated depression-like aspects of drug withdrawal. Further, chronic pretreatment with the atypical antipsychotic clozapine, that has some efficacy in the treatment of the depression-like symptoms of schizophrenia, attenuated nicotine and amphetamine withdrawal. Finally, a metabotropic glutamate 2/3 receptor antagonist reversed threshold elevations associated with nicotine withdrawal. The effects of these pharmacological manipulations are consistent with the altered neurobiology observed in drug withdrawal and depression. Thus, these data support the hypothesis of common substrates mediating the depressive symptoms of drug withdrawal and those seen in psychiatric patients. Accordingly, the anhedonic state associated with drug withdrawal can be used to study the neurobiology of anhedonia, and thus contribute to the identification of novel targets for the treatment of depression-like symptoms seen in various psychiatric and neurological disorders.

- by Neil Paterson
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- Depression, Schizophrenia, Serotonin, Glutamate

Introduction: The 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) is a popular recreational drug and a major source of substance abuse, which ultimately leads to sensations of well-being, elation and euphoria, moderate derealization/depersonalization, and cognitive disruptions, as well as intense sensory awareness. The mechanisms involved in memory impairment induced by MDMA are not completely understood.

Nevirapine (NVP) and efavirenz (EFV) belong to the class of anti-HIV drugs called non-nucleoside reverse transcriptase inhibitors (NNRTIs), commonly used as part of highly active antiretroviral therapy (HAART). Although the HAART is able to bring down viral load to undetectable levels and restore immune function, their prolonged use causes several adverse effects. It has been demonstrated that both NVP and EFV are able to cross the blood-brain barrier, causing important central nervous system-related side effects. Thus, this study investigated the effects of chronic administration of EFV (10 mg/kg) and NVP (3.3 mg/kg) in mice submitted to two distinct series of experiments, which aimed to evaluate: (1) the emotional behavior (elevated plus-maze, forced swimming, and open-field test) and (2) the cognitive performance (object recognition and inhibitory avoidance test) of mice. Our results demonstrated that EFV, but not NVP, reduced the exploration to open arms in the elevated plus-maze test. Neither NVP nor EFV altered mouse behavior in the forced swimming and open-field tests. Both drugs reduced the recognition index in the object recognition test, but only EFV significantly impaired the aversive memory assessed in the inhibitory avoidance test 24 h after training. In conclusion, our findings point to a genuine anxiogenic-like effect to EFV, since it reduced exploration to open arms of elevated plus-maze test without affecting spontaneous locomotion. Additionally, both drugs impaired recognition memory, while only the treatment with EFV impaired significantly aversive memory.

- by Vanessa Andrade and +1
- •
- Cognition, Recognition memory, Anxiety, Mice

Objectives To compare the clinical characteristics and the long-term outcome of a large series of patients with blepharospasm (BS) treated with the two most used brands of BoNT-A over the last 15 years. Methods We have reviewed the clinical charts of 128 patients with BS who received botulinum neurotoxin (BoNT) in 1341 treatments (Botox in 1009, Dysport in 332) over the last 15 years. Results Mean dose per session was 34U ± 15 for Botox and 152U ± 54 for Dysport. Mean latency of clinical effect was 4.5 ± 4.6 days for Botox and 5.0 ± 5.7 days for Dysport (P [ 0.05). Mean duration of clinical improvement was higher for Dysport than Botox: 80.1 ± 36.3 and 66.2 ± 39.8 days, respectively (P \ 0.01). In a six-point scale (0: no efficacy, 6: remission of BS), the mean efficacy of both treatments was 3.60 ± 1.3; 3.51 ± 1.4 (Botox) and 3.85 ± 1.2 (Dysport), P \ 0.01. The doses of Botox (b = 0.40) and Dysport (b = 0.16) were significantly increased over time. Side effects occurred in 325 out of 1341 treatments (24.2%): 21.8% of the patients who had received Botox, and in 31.6% of those who had received Dysport (P \ 0.01). Conclusions Both brands are effective and safe in treating blepharospasm; efficacy is long lasting. The differences in outcome and side effects suggest that, albeit the active drug is the same, Botox and Dysport should be considered as two different drugs.

- by Alberto Albanese and +1
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- Treatment, Treatment Outcome, Adolescent, Child

Background: This study documents cycad-human relationships in Mexico, Belize, Guatemala, El Salvador, and Honduras over the last 6000 years. The impetus was acute need for a better understanding of previously undocumented uses of cycads in this region, and the need to improve cycad conservation strategies using ethnobotanical data. We hypothesized that cycads are significant dietary items with no long-term neurological effects, are important to religious practice, and contribute to cultural identity and sense of place, but that traditional knowledge and uses are rapidly eroding. Guiding questions focused on nomenclature, food and toxicity, relationships to palms and maize, land management issues, roles in religious ceremony, and medicinal uses, among others, and contributions of these to preservation of cycads. Methods: From 2000 to 2017, the authors conducted 411 semi-structured ethnographic interviews, engaged in participant-observation in Mexican and Honduran communities, and carried out archival research and literature surveys. Results: We documented 235 terms and associated uses that 28 ethnic groups have for 57 species in 19 languages across 21 Mexican states and 4 Central American nations. Carbohydrate-rich cycads have been both famine foods and staples for at least six millennia across the region and are still consumed in Mexico and Honduras. Certain parts are eaten without removing toxins, while seed and stem starches are detoxified via several complex processes. Leaves are incorporated into syncretic Roman Catholic-Mesoamerican religious ceremonies such as pilgrimages, Easter Week, and Day of the Dead. Cycads are often perceived as ancestors and protectors of maize, revealing a close relationship between both groups. Certain beliefs and practices give cycads prominent roles in conceptions of sense of place and cultural heritage. Conclusions: Cycads are still used as foods in many places. Though they do not appear to cause long-term neurological damage, their health effects are not fully understood. They are often important to religion and contribute to cultural identity and sense of place. However, because most traditional knowledge and uses are rapidly eroding, new community-based biocultural conservation efforts are needed. These should incorporate tradition where possible and seek inspiration from existing successful cases in Honduras and Mexico.

- by Richard Kostrzewa
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- Neurotoxicity, Protein Aggregation, Neurotoxins, Nerve Regeneration

There is an increasing body of evidence on the possible environmental influence on neurodevelopmental and neurodegenerative disorders. Both experimental and epidemiological studies have demonstrated the distinctive susceptibility of the developing brain to environmental factors such as lead, mercury and polychlorinated biphenyls at levels of exposure that have no detectable effects in adults. Methylmercury (MeHg) has long been known to affect neurodevelopment in both humans and experimental animals. Neurobehavioural effects reported include altered motoric function and memory and learning disabilities. In addition, there is evidence from recent experimental neurodevelopmental studies that MeHg can induce depression-like behaviour. Several mechanisms have been suggested fromin vivo- andin vitro-studies, such as effects on neurotransmitter systems, induction of oxidative stress and disruption of microtubules and intracellular calcium homeostasis. Recentin vitro data show that very low levels of MeHg can inhibit neuronal differentiation of neural stem cells. This review summarises what is currently known about the neurodevelopmental effects of MeHg and consider the strength of different experimental approaches to study the effects of environmentally relevant exposurein vivo andin vitro.

- by Natalia Manzo
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- Human Development, Neurochemistry, Calcium, Neural stem cell

Investigating histamine through elevated IgE indicated pollen, food allergy and
infection in an earlier case study following five acute psychosis (AP) episodes[1]. A
sixth AP episode two-years later in spring provided opportunity for quantitative faecal
microbial investigation (QFMI). Protozoans Giardia sp. and Blastocystis sp. were
consistent with earlier findings, however anomalous Streptococcus spp. (SS)
overgrowth provided a new line of enquiry.
Exacerbating stool symptoms preceded AP. Post-AP symptoms included fatigue and
poor concentration. QFMI seven months post-AP identified very high oral SS 84%
(normal range [NR] <5%,) and very low Escherichia coli (E. coli) 16% (NR 70-
90%). SS are described as potent producers of only D- and L-Lactic acid from
glucose[2]. Limiting glucose/carbohydrates helped reduce SS from 84% to 16% (NR
<5%) of bacterial aerobes (BA) within five months, vastly increasing energy and
mental clarity.
SS/Enterococcus spp. at 95% (NR<5%) has been correlated with D-Lactic acidosis
(DLA)[3]. Symptoms of both DLA and AP are strikingly similar. Uribarri[4] suggested
either D-lactate as a direct neurotoxin independent of acidosis or other compounds
such as histamine may be needed, a link to earlier findings. Importantly, abnormally
high SS and other BA were historically considered causal in psychiatric presentations
(species-specific treatment of BA resolved psychiatric symptoms)[5].
Faecal PCR testing reveals major enteric pathogens, however QFMI is required
to ascertain BA SS., E. Coli and anaerobe imbalance. Timely investigation informs
relevant treatment to restore combined gastrointestinal and mental health and
strengthen innate immunity.
References
1. Lee, S. Cumulative histamine in psychosis and spring mania. Sum of insidious pollen, food
allergy and/or pathogenic parasites. (Abstract only) Early Intervention in Psychiatry 2012.. 6: p.
56-56
2. Sheedy, J.R., et al., Increased d-lactic Acid intestinal bacteria in patients with chronic fatigue
syndrome. In Vivo, 2009. 23(4): p. 621-8.
3. Cosford, R.E., Immune Cross Reactions and metabolic acidosis in children with autism in
Science of Nutrition in Medicine and Healthcare Conference 2013: Sydney.
4. Uribarri, J., M.S. Oh, and H.J. Carroll, D-lactic acidosis. A review of clinical presentation,
biochemical features, and pathophysiologic mechanisms. Medicine (Baltimore), 1998. 77(2): p.
73-82.
5. Cotton, H.A., The defective delinquent and insane: The relation of focal infections to their
causation, treatment and prevention. 1921, Princeton, NJ: Princeton University Press. 201p.

- by Sally Lee
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- Psychosis, Neurotoxicity, Giardiasis, Blastocystis