Nadja Schroder - Academia.edu (original) (raw)

Papers by Nadja Schroder

Experimental Neurology, Oct 1, 1997

In the present study we demonstrate that propionic acid (PA), a metabolite that accumulates in la... more In the present study we demonstrate that propionic acid (PA), a metabolite that accumulates in large amounts in propionic acidemia, is able to decrease in vitro incorporation of [32P]ATP into neurofilament subunits (NF-M and NF-L) and alpha- and beta-tubulin. Considering that the endogenous phosphorylating system associated with the cytoskeletal fraction contains cAMP-dependent protein kinase (PKA), Ca2+/calmodulin protein kinase II (CaMKII), and protein phosphatase 1 (PP1), we first assayed the effect of the acid on the kinase activities by using the specific activators cAMP and Ca2+/calmodulin or the inhibitors PKAI or KN-93 for PKA and CaMKII, respectively. Results demonstrated that the acid totally inhibited the stimulatory effect of cAMP and interfered with the inhibitory effect of PKAI. In addition, PA partially prevented the stimulatory effect of Ca2+/calmodulin and interfered with the effect of KN-93. In addition, we demonstrated that PA totally inhibited in vitro dephosphorylation of neurofilament subunits and tubulins mediated by PP1 in brain slices pretreated with the acid. Taken together, these results demonstrate that PA inhibits the in vitro activities of PKA, CaMKII, and PP1 associated with the cytoskeletal fraction of the cerebral cortex of rats. This study suggests that PA at the same concentrations found in tissues from propionic acidemic children may alter phosphorylation of cytoskeletal proteins, which may contribute to the neurological dysfunction characteristic of propionic acidemia.

Archives of Gerontology and Geriatrics, Mar 1, 2022

OBJECTIVE To systematically review the acute effects of physical exercise on memory in healthy el... more OBJECTIVE To systematically review the acute effects of physical exercise on memory in healthy elderly people. METHODS The present study consists of a systematic review based on the criteria of the Preferred Reporting Items for Systematic Reviews and Meta - Analyzes (PRISMA). Searches were carried out in the health databases: PubMed (Medline); ScienceDirect (Elsevier); SciELO, Cochrane and LILACS, including articles published until April 2021. The included studies should be randomized clinical trials in healthy elderly populations, have acute physical exercise as an intervention compared to another type of exercise or to a control session, and assess memory as an outcome. RESULTS A total of 3711 records were found in the databases. After reading titles and abstracts, 27 full texts of studies were selected. A total of 10 records met the inclusion criteria and were considered eligible for qualitative analysis. The total sample consisted of 465 healthy individuals, of both sexes, aged between 60 and 95 years. The aerobic and resistance exercises performed at low (7-11 Borg scale, 54% FCM or 40-54% 1RM) and moderate intensities (12-15 Borg scale, 50-70% FCM and 55-75% 1RM) lead to memory improvement in cognitively healthy elderly people. CONCLUSIONS The paucity of studies with this population, using higher exercise intensities, as well as a reduced variety of memory tests, were limiting factors. Maintaining a training routine is important, in order to preserve physical and mental health. More studies addressing the effects of exercise protocols in healthy individuals are warranted.

Frontiers in Pharmacology, Jun 28, 2017

Gene expression related to the formation and modification of memories is regulated epigenetically... more Gene expression related to the formation and modification of memories is regulated epigenetically by chromatin remodeling through histone acetylation. Memory formation and extinction can be enhanced by treatment with inhibitors of histone deacetylases (HDACs). The basolateral amygdala (BLA) is a brain area critically involved in regulating memory for inhibitory avoidance (IA). However, previous studies have not examined the effects of HDAC inhibition in the amygdala on memory for IA. Here we show that infusion of an HDAC inhibitor (HDACi), trichostatin A (TSA), into the BLA, enhanced consolidation of IA memory in rats when given at 1.5, 3, or 6 h posttraining, but not when the drug was infused immediately after training. In addition, intra-BLA administration of TSA immediately after retrieval delayed extinction learning. Moreover, we show that intra-BLA TSA in rats given IA training increased the levels of brain-derived neurotrophic factor in the dorsal hippocampus, but not in the BLA itself. These findings reveal novel aspects of the regulation of fear memory by epigenetic mechanisms in the amygdala.

Neurofunctional deficits in mice induced by postnatal iron exposure: dose, time and MPTP interact... more Neurofunctional deficits in mice induced by postnatal iron exposure: dose, time and MPTP interactions. In: Palomo T, Beninger RJ, Archer T (eds). Neurdegerative Brain Disorders

Journal of Neurochemistry, May 24, 2021

The science community has lost one of its giants. Neurobiologist Ivan Izquierdo died on February ... more The science community has lost one of its giants. Neurobiologist Ivan Izquierdo died on February 9th at his home in Porto Alegre, in the southern state of Rio Grande do Sul, Brazil. Ivan was recognized primarily for his role in uncovering the molecular and neurochemical mechanisms underlying different stages of memory formation and extinction in several brain areas.

Introduction: Psychiatric disorders are among the most common diseases and represent an important... more Introduction: Psychiatric disorders are among the most common diseases and represent an important public health problem. The neurobiological processes implicated in the pathophysiology of neuropsychiatric disorders are not fully known. Exposure to adverse events in early life increases the risk of developing neuropsychiatric conditions in adulthood, including affective disorders and psychosis. In rodents, maternal separation (MS) is commonly used as a model of exposure to stress in early life. MS may cause long-term effects on brain function, including cellular, neurochemical and behavioral changes. The involvement of proinflammatory cytokines in neuropsychiatric disorders has attracted increasing interest from researchers. Topiramate is an antiepileptic drug that has proven to exhibit neuroprotective properties in animal models of brain injury, reducing neuronal damage in animal models of neonatal hypoxic ischemia and attenuating memory deficits. Objectives: To investigate the effect of Topiramate (Top) in reversing cognitive impairment in rats submitted to neonatal stress induced by MS and compare with Valproic Acid (Val), which was previously studied by our research group. Furthermore, to investigate the effects of neonatal stress with and without treatment with Val and Top on BDNF, TNF-α, and Interleukin 10 (IL-10) levels. Methodology: Study on animal model of stress exposure in neonatal period (method of MS), in male rats. Treatment with Top and Val in adulthood: one group received 10mg/kg of Top orally once a day for 14 days, the other group received 100mg/kg of Top in the same period, another group received Val 200mg/kg orally in the same period, and the other group received the same corresponding amount in milliliters also orally of saline solution (control group). Behavioral tests (motor/exploratory activity, recognition memory), and analyzes of BDNF, TNF-α , and IL-10 levels were performed in adulthood. Results: The MS during the neonatal period causes memory impairment in adult rats. The treatment in adults with Top caused injury to memory when used, independently of maternal separation. Likewise, it also failed to reverse the damage caused by MS. Pharmacological treatment with Val in adulthood reversed long-term (LTM) memory deficits induced by MS and caused an improvement in short-term memory (STM) in rats separated from the mother. The MS induced a significant increase in IL-10 when the separated-saline (MS-Sal) was compared with the control group (non-separated-saline, NS-Sal). Statistical comparisons of TNF-α levels, indicated that the group subjected to MS which received saline (MS-Sal) showed a significant increase in the levels of TNF-α in the hippocampus when compared with the control group. Similarly, the levels of TNF-α in the group MS-Sal were also increased in cortex, compared to NS-Sal group. The MS induced a significant decrease in BDNF levels in the hippocampus, when the group MS-Sal was compared with the control group. No statistically significant difference was observed in the comparison of BDNF in prefrontal cortex. Conclusions: MS leads to persistent memory deficits and increases levels of the anti-inflammatory cytokine, IL-10, and of the pro-inflammatory cytokine, TNF-α, and decreases levels of BDNF in adulthood. Val partially alleviated these memory deficits, while Top was ineffective. Surprisingly, the two drugs were able to recover levels of cytokines in brain regions studied.

Cns & Neurological Disorders-drug Targets, Jun 1, 2023

: It is believed that degenerative conditions that give rise to neurological diseases may share a... more : It is believed that degenerative conditions that give rise to neurological diseases may share an abnormal influx of Ca2+, mainly through glutamate receptors. Current research on the glutamatergic system indicates that the N-methyl-D-aspartate receptor (NMDAR) is not the only receptor permeable to Ca2+. Under certain conditions, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) are able to rapidly and potently mediate a neurotoxic Ca2+ influx. AMPARs are encoded by four genes designated GluR 1-4. The presence of the edited GluA2 subunit makes the heteromeric AMPAR impermeable to Ca2+ (CI-AMPAR's). On the other hand, the lack of GluA2 or disruptions in its post-translational editing result in Ca2+-permeable AMPA receptors (CP-AMPARs). In addition to triggering behavioral changes, the increase in CP-AMPARs is documented in several neurodegenerative, neuroinflammatory and neurotoxic conditions, demonstrating that AMPAR changes may play a role in the emergence and evolution of pathological conditions of the central nervous system (CNS). Seeking to better understand how CP-AMPARs influence CNS neuropathology, and how it may serve as a pharmacological target for future molecules, in this article, we summarize and discuss studies investigating changes in the composition of AMPARs and their cellular and molecular effects, to improve the understanding of the therapeutic potential of the CP-AMPAR in neurodegenerative, neurotoxic and neuroinflammatory diseases.

Neurochemical Research, May 1, 1996

Neurofilaments subunits (NF-H, NF-M, NF-L) and glial fibrillary acidic protein (GFAP) were invest... more Neurofilaments subunits (NF-H, NF-M, NF-L) and glial fibrillary acidic protein (GFAP) were investigated in the hippocampus of rats after distinct periods of reperfusion (1 to 15 days) following 20 min of transient global forebrain ischernia in the rat. In vitro [14Ca]leucine incorporation was not altered until 48 h after the ischemic insult, however concentration of intermediate filament subunits significantly decreased in this period. Three days after the insult, leucine incorporation significantly increased while the concentration NF-H, NF-M, and NF-L were still diminished after 15 days of reperfusion. In vitro incorporation of 32p into NF-M and NF-L suffered immediately after ischemia, but returned to control values after two days of reperfusion. GFAP levels decreased immediately after ischemia but quickly recovered and significantly peaked from 7 to 10 days after the insult. These results suggest that transient ischemia followed by reperfusion causes proteolysis of intermediate filaments in the hippocampus, and that proteolysis could be facilitated by diminished phosphorylation levels of NF-M and NF-L.

Research Square (Research Square), Apr 3, 2023

Lipocalin 2 (LCN2) controls iron levels, in ammation, cell death and is associated with neurodege... more Lipocalin 2 (LCN2) controls iron levels, in ammation, cell death and is associated with neurodegenerative conditions. Moreover, obesity and insulin resistance modulate LCN2 expression. In this study we explored the effects of neonatal iron overload and a high-fat diet (HFD) after weaning on gene expression of LCN2, its receptor 24p3R, and the pro-apoptotic BCL-2-interacting mediator of cell death (BIM), besides evaluating the levels of LCN2 and of the anti-apoptotic protein B-cell lymphoma 2 (BCL2). Male Wistar rats received vehicle or carbonyl iron (30mg/kg) from the 12th to the 14th postnatal day. After weaning animals were treated with a HFD or a standard diet. At 9 months animal were euthanized and the hippocampus collected for RT-qPCR analysis of gene expression and Western Blot analysis of protein levels. The results indicate that iron overload during the neonatal period induced an increase in the gene expression for LCN2, its receptor 24p3R, and BIM, besides an increase of LCN2 protein levels. The exposure to a HFD throughout life, increased animals' body weight and led to the decrease on BIM mRNA and BCl2 protein levels. Moreover, the combination of iron overload and HFD exacerbated the increase in LCN2 levels. In conclusion, the results of this study give support to the hypothesis that early life iron overload and a high fat diet are potential risk factors (each one alone and together) for neuronal death mediated by LCN2.

Alzheimers & Dementia, Jul 1, 2010

DOAJ (DOAJ: Directory of Open Access Journals), 2007

Increasing evidence has indicated that iron plays an important role in the pathogenesis of neurod... more Increasing evidence has indicated that iron plays an important role in the pathogenesis of neurodegenerative disorders. The aim of this article is to review aspects related to iron absortion, transport and storage in the human body. Additionally, the role of iron in oxidative stress in the central nervous system, and its implications to prevalent neurodegenerative disorders, with special reference to Alzheimer's dementia and Parkinson's disease are discussed.

Frontiers in Human Neuroscience, Apr 27, 2023

Editorial on the Research Topic The impacts of iron accumulation on cognitive impairments

European journal of nutrition, Mar 18, 2021

Purpose To investigate the effects of lipoic acid (LA) supplementation during adulthood combined ... more Purpose To investigate the effects of lipoic acid (LA) supplementation during adulthood combined with supplementation later in life or LA administration only at old age on age-induced cognitive dysfunction, mitochondrial DNA deletions, caspase 3 and antioxidant response enzymes expression in iron-treated rats. Methods Male rats were submitted to iron treatment (30 mg/kg body wt of Carbonyl iron) from 12 to 14th post-natal days. Iron-treated rats received LA supplementation (50 mg/kg, daily) in adulthood and old age or at old age only for 21 days. Memory, mitochondrial DNA (mtDNA) complex I deletions, caspase 3 mRNA expression and antioxidant response enzymes mRNA expression were analyzed in the hippocampus. Results LA administration in adulthood combined with treatment later in life was able to reverse age-induced effects on object recognition and inhibitory avoidance memory, as well as on mtDNA deletions, nuclear factor (erythroid-derived 2)-like 2 (Nrf2) expression, and antioxidant enzymes disruption induced by iron in aged rats. LA treatment only at old age reversed iron-induced effects to a lesser extent when compared to the combined treatment. Conclusion The present findings support the view that LA supplementation may be considered as an adjuvant against mitochondrial damage and cognitive decline related to aging and neurodegenerative disorders.

Behavioural Brain Research

Behavioural Brain Research, 2022

Clinical and preclinical evidence has indicated that estrogen depletion leads to memory impairmen... more Clinical and preclinical evidence has indicated that estrogen depletion leads to memory impairments and increases the susceptibility to neural damage. Here, we have sought to investigate the effects of Cannabidiol (CBD) a non-psychotomimetic compound from Cannabis sativa, on memory deficits induced by estrogen depletion in rats, and its underlying mechanisms. Adult rats were subjected to bilateral ovariectomy, an established estrogen depletion model in rodents, or sham surgery and allowed to recover for three weeks. After that, they received daily injections of CBD (10 mg/kg) for fourteen days. Rats were tested in the inhibitory avoidance task, a type of emotionally-motivated memory. After behavioral testing they were euthanized, and their hippocampi were isolated for analysis of components of the Akt/GSK3β survival pathway and the antiapoptotic protein Bcl2. Results revealed that ovariectomy impaired avoidance memory, and CBD was able to completely reverse estrogen depletion-induced memory impairment. Ovariectomy also reduced Akt/GSK3β pathway's activation by decreasing the phosphorylation levels of Akt and GSK3β and Bcl2 levels, which were ameliorated by CBD. The present results indicate that CBD leads to a functional recovery accompanied by the Akt/GSK3β survival pathway's activation, supporting its potential as a treatment for estrogen decline-induced deterioration of neural functioning and maintenance.

European Journal of Nutrition, 2021

Neurobiology of Learning and Memory, 2021

Estrogens, particularly 17β-estradiol (estradiol, E 2), regulate memory formation. E2 acts throug... more Estrogens, particularly 17β-estradiol (estradiol, E 2), regulate memory formation. E2 acts through its intracellular receptors, estrogen receptors (ER) ERα and ERβ, as well as a recently identified G protein-coupled estrogen receptor (GPER). Although the effects of E2 on memory have been investigated, studies examining the effects of GPER stimulation are scarce. Selective GPER agonism improves memory in ovariectomized female rats, but little information is available regarding the effects of GPER stimulation in male rodents. The aim of the present study was to investigate the effects of the GPER agonist, G1, on consolidation and reconsolidation of inhibitory avoidance (IA) and object recognition (OR) memory in male rats. Animals received vehicle, G1 (15, 75, 150 µg/ kg; i.p.), or the GPER antagonist G15 (100 µg/kg; i.p.) immediately after training, or G1 (150 µg/kg; i.p.) 3 or 6 h after training. To investigate reconsolidation, G1 was administered immediately after IA retention Test 1. Results indicated that G1 administered immediately after training at the highest dose enhanced both OR and IA memory consolidation, while GPER blockade immediately after training impaired OR. No effects of GPER stimulation were observed when G1 was given 3 or 6 h after training or after Test 1. The present findings provide evidence that GPER is involved in the early stages of memory consolidation in both neutral and emotional memory tasks in male adult rats.

Neuroscience, Jan 22, 2015

Iron overload contributes to the development of neurodegeneration and the exacerbation of normal ... more Iron overload contributes to the development of neurodegeneration and the exacerbation of normal apoptosis rates, largely due to its participation in the Fenton reaction and production of reactive oxygen species (ROS). Mitochondria constitute the major intracellular source of ROS and the main target of attack by free radicals. They are dynamic organelles that bind (fusion) and divide (fission) in response to environmental stimuli, developmental status, and energy needs of the cells. Sulforaphane (SFN) is a natural compound that displays antioxidant and anti-inflammatory activities. This study aims to investigate the effects of SFN on memory deficits and changes in markers of mitochondrial function, DNM1L and OPA1, and the synaptic marker, synaptophysin, induced by neonatal iron treatment. Male rats received vehicle or carbonyl iron (30mg/kg) from the 12th to the 14th postnatal day. In adulthood, they were treated with saline or SFN (0.5 or 5 mg/kg) for 14 days every other day. Memor...