Monica Vianna - Academia.edu (original) (raw)

Papers by Monica Vianna

Frontiers in Pharmacology

Atrazine and Diuron are widely used herbicides. The use of pesticides contaminates the aquatic en... more Atrazine and Diuron are widely used herbicides. The use of pesticides contaminates the aquatic environment, threatening biodiversity and non-target organisms such as fish. In this study, we investigated the effects of acute exposure for 96 h hours to atrazine and diuron commercial formulations in zebrafish (Danio rerio, wild-type AB) embryos and larvae and adult stages. We observed a significant concentration-dependent survival decrease and hatching delays in animals exposed to both herbicides and in the frequency of malformations compared to the control groups. Morphological defects included cardiac edema, tail reduction, and head malformation. At 7 days post-fertilization (dpf), atrazine exposure resulted in a reduction in the head length at 2, 2.5, and 5 mg/L and increased the ocular distance at 1, 2, 2.5, and 5 mg/L atrazine when compared to controls. At the same age, diuron increased the ocular distance in animals exposed to diuron (1.0 and 1.5 mg/L) and no effects were observe...

Exposição a um novo ambiente previamente a um teste de retenção de memória facilita a evocação. F... more Exposição a um novo ambiente previamente a um teste de retenção de memória facilita a evocação. Foram investigados os mecanismos hipocampais envolvidos no efeito de intensificação causado pela novidade sobre a evocação da memória. Ratos Wistar machos com o hipocampo canulado foram expostos a um ambiente desconhecido 0, 1, 2, 4 ou 6h ou 2 vezes 1 e 4h antes do teste de retenção em esquiva inibitória. Antes da exposição ao novo ambiente, foram infundidos bilateralmente com veículo, antagonista de receptores NMDA (APV), antagonista da proteína kinase (RpcAMPS) ou inibidor da MAPK kinase (PD098095); foi realizado Western Blot de MAPKs totais e fosforiladas, phospho-CREB, CREB e phospho-αCaMKII de extrados do hipocampo. Novidade 0, 1 e 2 h antes do teste facilitou evocaηão, tal efeito foi bloqueado por APV e PD098095, houve também aumento de phospho-p42 e p-p44 MAPKs (medidas logo após evocação), o qual não foi bloqueado por APV e PD098095. Tais resultados indicam que novidade ativa p42 e p44 MAPKs que são necessárias, mas não no momento da evocação, junto com receptores NMDA para a facilitação causada pela novidade. (CNPq, PRONEX).

Cellular and Molecular Neurobiology, 2002

1. It has been discussed for over 100 years whether short-term memory (STM) is separate from, or ... more 1. It has been discussed for over 100 years whether short-term memory (STM) is separate from, or just an early phase of, long-term memory (LTM). The only way to solve this dilemma is to find out at least one treatment that blocks STM while keeping LTM intact for the same task in the same animal. 2. The effect of a large number of treatments infused into the hippocampus, amygdala, and entorhinal, posterior parietal or prefrontal cortex on STM and LTM of a one-trial stepdown inhibitory avoidance task was studied. The animals were tested at 1.5 h for STM, and again at 24 h for LTM. The treatments were given after training. 3. Eleven different treatments blocked STM without affecting LTM. Eighteen treatments affected the two memory types differentially, either blocking or enhancing LTM alone. Thus, STM is separate from, and parallel to the first hours of processing of, LTM of that task. 4. The mechanisms of STM are different from those of LTM. The former do not include gene expression or protein synthesis; the latter include a double peak of cAMP-dependent protein kinase activity, accompanied by the phosphorylation of CREB, and both gene expression and protein synthesis. 5. Possible cellular and molecular events that do not require mRNA or protein synthesis should account for STM. These might include a hyperactivation of glutamate AMPA receptors, ribosome changes, or the exocytosis of glycoproteins that participate in cell addition.

Neurochemical Research, 2002

Memory retrieval is a fundamental component or stage of memory processing. In fact, retrieval is ... more Memory retrieval is a fundamental component or stage of memory processing. In fact, retrieval is the only possible measure of memory. The ability to recall past events is a major determinant of survival strategies in all species and is of paramount importance in determining our uniqueness as individuals. Most biological studies of memory using brain lesion and/or gene manipulation techniques cannot distinguish between effects on the molecular mechanisms of the encoding or consolidation of memories and those responsible for their retrieval from storage. Here we examine recent findings indicating the major molecular steps involved in memory retrieval in selected brain regions of the mammalian brain. Together the findings strongly suggest that memory formation and retrieval may share some molecular mechanisms in the hippocampus and that retrieval initiates extinction requiring activation of several signaling cascades and protein synthesis.

Hippocampus, 2002

Information storage in the brain is a temporally graded process involving different memory types ... more Information storage in the brain is a temporally graded process involving different memory types or phases. It has been assumed for over a century that one or more short-term memory (STM) processes are involved in processing new information while long-term memory (LTM) is being formed. Because brain-derived neutrophic factor (BDNF) modulates both short-term synaptic function and activity-dependent synaptic plasticity in the adult hippocampus, we examined the role of BDNF in STM and LTM formation of a hippocampal-dependent one-trial fear-motivated learning task in rats. Using a competitive RT-PCR quantitation method, we found that inhibitory avoidance training is associated with a rapid and transient increase in BDNF mRNA expression in the hippocampus. Bilateral infusions of function-blocking anti-BDNF antibody into the CA, region of the dorsal hippocampus decreased extracellular signal-regulated kinase 2 (ERK2) activation and impaired STM retention scores. Inhibition of ERK1/2 activation by PD098059 produced similar effects. In contrast, intrahippocampal administration of recombinant human BDNF increased ERK1/2 activation and facilitated STM. The infusion of anti-BDNF antibody impaired LTM when given 15 min before or 1 and 4 hr after training, but not at 0 or 6 hr posttraining, indicating that two hippocampal BDNF-sensitive time windows are critical for LTM formation. At the same time points, PD098059 produced no LTM deficits. Thus, our results indicate that endogenous BDNF is required for both STM and LTM formation of an inhibitory avoidance learning. Additionally, they suggest that this requirement involves ERK1/2-dependent and -independent mechanisms.

Neurobiology of Learning and Memory, 2009

The behavioral tasks aiming to evaluate learning and memory mechanisms currently available to zeb... more The behavioral tasks aiming to evaluate learning and memory mechanisms currently available to zebrafish (Danio rerio) involve long training sessions frequently along multiple days and are based on shuttle box or active-avoidance protocols, preventing a detailed analysis of cellular and molecular time-dependent processes involved in memory acquisition and consolidation. In order to explore zebrafish&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s potential contribution to the characterization of the molecular machinery underlying learning and memory rapidly acquired and reliable paradigms are necessary. In this study we present a rapid and effective learning protocol in a single-trial inhibitory avoidance in zebrafish. In a simple apparatus, adult animals learned to refrain from swimming from a white into a dark compartment in order to avoid an electric shock during a single-trial training session that lasted less than 2 min. The resulting memory is robust, long-lasting and sensitive to NMDA-receptor antagonist MK-801 given in the tank water immediately after training. Experiments aiming to further characterize the events underlying memory formation, retrieval or extinction or those looking for cognitive profiling of mutants, neurotoxicological studies and disease models may benefit from this task, and together with complementary strategies available for zebrafish may significantly improve our current knowledge on learning and memory mechanisms.

European Journal of Neuroscience, 2001

Rats exposed to a novel environment just prior to or 1±2 h, but not 4 or 6 h, before retention te... more Rats exposed to a novel environment just prior to or 1±2 h, but not 4 or 6 h, before retention testing exhibited an enhanced retrieval of a one-trial inhibitory avoidance training. The bilateral intrahippocampal infusion of PD098059, an inhibitor of mitogenactivated protein kinase (MAPK), the speci®c upstream activator of p42 and p44 MAPKs, given 10 min before the exposure to the novel environment, blocked the enhancing effect of novelty on memory retrieval. In addition, prenovelty infusion of DL-2amino-5-phosphonovalerate (APV), an antagonist of glutamate NMDA receptors, produced similar effects. The exposure to the novel environment is associated with an activation of p42 and p44 MAPKs and an increase in the phosphorylation state of the transcription factor cAMP response element binding protein (CREB). No changes were observed in cAMP-dependent protein kinase (PKA) activity or in a-CAMKII activation. Taken together, our results indicate that novelty activates hippocampal MAPKs, which are necessary, along with glutamate NMDA receptors, for the enhancing effect of novelty on retrieval.

Brain Research, 2003

Adult male rats bilaterally implanted with guide canullae aimed either at the dorsal hippocampus ... more Adult male rats bilaterally implanted with guide canullae aimed either at the dorsal hippocampus (dHIP) or the basolateral nucleus of the amygdala (BLA) were trained in a step-down inhibitory avoidance task (IA) and tested for retention 24 h after training. Immediately after training, animals were given a bilateral infusion of the N-methyl-D-aspartate (NMDA) glutamate receptor antagonist D,L-2-amino-5-phosphonopentanoic acid (AP5) (5.0 microg) into the dHIP or the BLA. Both intrahippocampal and intraamygdala infusions of AP5 blocked IA retention. Preexposure to the training box, but not to a different environment 24 h prior to training prevented the impairing effect of intrahippocampal infusion of AP5 on retention. Preexposure did not affect the retention impairment induced by intraamygdala infusion of AP5. These data suggest that hippocampal NMDA receptors might be involved in the contextual and spatial aspects, while amygdalar NMDA receptors might be involved in the aversive aspects of memory for IA.

Behavioural Brain Research, 1999

It has been assumed for over a century that short-term memory (STM) processes are in charge of co... more It has been assumed for over a century that short-term memory (STM) processes are in charge of cognition while long-term memory (LTM) is being formed, a process that takes hours. A major question is whether STM is merely a step towards LTM, or a separate entity. Recent experiments have shown that many treatments with specific molecular actions given into the hippocampus, entorhinal or parietal cortex immediately after one-trial avoidance training can effectively block STM without affecting LTM formation. This shows that STM and LTM involve separate mechanisms. Some treatments even affect STM and LTM in opposite directions. Others, however, influence both memory types similarly, suggesting links between the two both at the receptor and at the post-receptor level. Drug effects on working memory (WM) were also studied. In some brain regions WM is affected by receptor blockers that alter either STM or LTM; in others it is not. This suggests links between the three memory types at the receptor level. The anterolateral prefrontal cortex is crucial for WM and LTM but is not involved in STM. The hippocampus, entorhinal and parietal cortex are crucial for the three types of memory, in some cases using different receptors for each. The amygdala is not involved in WM or STM, but it plays a key role in the modulation of the early phase of LTM.

Behavioral Neuroscience, 2004

The gamma aminobutyric acid-A (GABA A) agonist, muscimol, the glutamate N-methyl-D-aspartate (NMD... more The gamma aminobutyric acid-A (GABA A) agonist, muscimol, the glutamate N-methyl-D-aspartate (NMDA) receptor antagonist, D-2-amino-5-phosphonopentanoic acid (AP5), and the inhibitor of the extracellularly regulated kinases (ERKs), U0 126, cause retrograde amnesia when administered to the hippocampus. In the present study, the authors found that they all cause retrograde amnesia for 1-trial inhibitory avoidance, not only when infused into the dorsal CA1 region of the hippocampus, but also when infused into the basolateral amygdala or the entorhinal, parietal, and posterior cingulate cortices. The posttraining time course of the effect of each drug was, however, quite different across brain structures. Thus, in all of them, NMDA receptors and the ERK pathway are indispensable for memory consolidation, and GABA A receptor activation inhibits memory consolidation; but in each case, their influence is interwoven differently.

Anais da Academia Brasileira de Ciências, 2004

Memory is measured by measuring retrieval. Retrieval is often triggered by the conditioned stimul... more Memory is measured by measuring retrieval. Retrieval is often triggered by the conditioned stimulus (CS); however, as known since Pavlov, presentation of the CS alone generates extinction. One-trial avoidance (IA) is a much used conditioned fear paradigm in which the CS is the safe part of a training apparatus, the unconditioned stimulus (US) is a footshock and the conditioned response is to stay in the safe area. In IA, retrieval is measured without the US, as latency to step-down from the safe area (i.e., a platform). Extinction is installed at the moment of the first unreinforced test session, as clearly shown by the fact that many drugs, including PKA, ERK and protein synthesis inhibitors as well as NMDA receptor antagonists, hinder extinction when infused into the hippocampus or the basolateral amygdala at the moment of the first test session but not later. Some, but not all the molecular systems required for extinction are also activated by retrieval, further endorsing the hyp...

Cellular and Molecular Neurobiology, 2005

1. Memory is assessed by measuring retrieval which is often elicited by the solely presentation o... more 1. Memory is assessed by measuring retrieval which is often elicited by the solely presentation of the conditioned stimulus (CS). However, as known since Pavlov, presentation of the CS alone generates extinction. 2. One-trial avoidance (IA) is a much used conditioned fear paradigm in which the CS is the safe part of a training apparatus, the unconditioned stimulus (US) is a footshock and the conditioned response (CR) is to stay in the safe area. Retrieval of the memory for the step-down version of this task is measured in the absence of the US, as latency to step-down from the safe area (i.e., a platform). 3. Extinction of the IA response is installed at the moment of the first non-reinforced test session, as clearly shown by the fact that many drugs, including PKA, ERK and protein synthesis inhibitors as well as NMDA receptor antagonists, hinder extinction when infused into the hippocampus or the basolateral amygdala at the moment of the first test session but not later. 4. Some, but not all the molecular systems required for extinction are also activated by retrieval, further endorsing the hypothesis that although retrieval is necessary for the generation of extinction this last process constitutes a new learning secondary to the non-reinforced expression of the original trace.

Neurotoxicity Research, 2002

Many, if not all psychiatric diseases are accompanied by memory disturbances, in particular, the ... more Many, if not all psychiatric diseases are accompanied by memory disturbances, in particular, the dementias, schizophrenia, and, to an extent, mood disorders. Anxiety and stress, on the other hand, cause important alterations of memory, particularly its retrieval. Here we discuss several new findings on the basic mechanisms of consolidation, retrieval and extinction of a prototype form of episodic memory in the rat: conditioned fear. The findings point the way for investigations on the pathology of these aspects of memory in health and disease. Emphasis is placed on the parallel processing Of retrieval in several cortical areas, on the links between retrieval and the onset of extinction, on the fact that extinction involves new learning requiring gene expression, and on the differences between the retrieval of recent or remote long-term memories.

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PeerJ, 2018

Parkinson's disease (PD) is the second most common neurodegenerative disorder. In addition to... more Parkinson's disease (PD) is the second most common neurodegenerative disorder. In addition to its highly debilitating motor symptoms, non-motor symptoms may precede their motor counterparts by many years, which may characterize a prodromal phase of PD. A potential pharmacological strategy is to introduce neuroprotective agents at an earlier stage in order to prevent further neuronal death. -acetylcysteine (NAC) has been used against paracetamol overdose hepatotoxicity by restoring hepatic concentrations of glutathione (GSH), and as a mucolytic in chronic obstructive pulmonary disease by reducing disulfide bonds in mucoproteins. It has been shown to be safe for humans at high doses. More recently, several studies have evidenced that NAC has a multifaceted mechanism of action, presenting indirect antioxidant effect by acting as a GSH precursor, besides its anti-inflammatory and neurotrophic effects. Moreover, NAC modulates glutamate release through activation of the cystine-glutam...

The Science of the total environment, Jan 15, 2018

Nickel is a heavy metal that, at high concentrations, leads to environmental contamination and ca... more Nickel is a heavy metal that, at high concentrations, leads to environmental contamination and causes health problems. We evaluated the effects of NiCl exposure on cognition and behavior in larval and adult zebrafish. Larval and adult zebrafish were exposed to NiCl concentrations (0.025, 2.0, 5.0, and 15.0mg/L) or water (control) in two treatment regimens: acute and subchronic. Larvae were exposed to NiCl for 2h (acute treatment: 5-day-old larvae treated for 2h, tested after treatment) or 11days (subchronic treatment: 11-day-old larvae treated since fertilization, tested at 5, 8 and 11days post-fertilization, dpf). Adults were exposed for 12h (acute treatment) or 96h (subchronic treatment) and were tested after the treatment period. In both regimens, exposed zebrafish showed concentration-dependent increases in body nickel levels compared with controls. For larvae, delayed hatching, decreased heart rate and morphological alterations were observed in subchronically treated zebrafish....

Neurochemical research, Jan 16, 2017

Presenilins are transmembrane proteases required for the proteolytic cleavage of Notch and also a... more Presenilins are transmembrane proteases required for the proteolytic cleavage of Notch and also act as the catalytic core of the γ-secretase complex, which is responsible for the final cleavage of the amyloid precursor protein into Amyloid-β (Aβ) peptides of varying lengths. Presenilin-1 gene (psen1) mutations are the main cause of early-onset autosomal-dominant Familial Alzheimer Disease. Elucidating the roles of Presenilin-1 and other hallmark proteins involved in Alzheimer's disease is crucial for understanding the disease etiology and underlying molecular mechanisms. In our study, we used a morpholino antisense nucleotide that targets exon 8 splicing site of psen1 resulting in a dominant negative protein previously validated to investigate behavioral and molecular effects in 5 days post fertilization (dpf) zebrafish larvae. Morphants showed specific cognitive deficits in two optomotor tasks and morphological phenotypes similar to those induced by suppression of Notch signali...

Aquatic Toxicology, 2016

Manganese (Mn) is an essential metal for organisms, but high levels can cause serious neurologica... more Manganese (Mn) is an essential metal for organisms, but high levels can cause serious neurological damage. The aim of this study was to evaluate the effects of MnCl2 exposure on cognition and exploratory behavior in adult and larval zebrafish and correlate these findings with brain accumulation of Mn, overall brain tyrosine hydroxylase (TH) levels, dopamine (DA) levels, 3,4-dihydroxyphenylacetic acid (DOPAC) levels and cell death markers in the nervous system. Adults exposed to MnCl2 for 4days (0.5, 1.0 and 1.5mM) and larvae exposed for 5days (0.1, 0.25 and 0.5mM) displayed decreased exploratory behaviors, such as distance traveled and absolute body turn angle, in addition to reduced movement time and an increased number of immobile episodes in larvae. Adults exposed to MnCl2 for 4days showed impaired aversive long-term memory in the inhibitory avoidance task. The overall brain TH levels were elevated in adults and larvae evaluated at 5 and 7 days post-fertilization (dpf). Interestingly, the protein level of this enzyme was decreased in larval animals at 10dpf. Furthermore, DOPAC levels were increased in adult animals exposed to MnCl2. Protein analysis showed increased apoptotic markers in both the larvae and adult nervous system. The results demonstrated that prolonged exposure to MnCl2 leads to locomotor deficits that may be associated with damage caused by this metal in the CNS, particularly in the dopaminergic system.

O sistema colinérgico é conhecido por sua participação no processamento da memória, e substâncias... more O sistema colinérgico é conhecido por sua participação no processamento da memória, e substâncias que afetem este sistema, ativando-o ou inibindo-o, são instrumentos úteis para estes estudos. Do veneno de algumas cobras da família elapideae, gênero Dendroaspis (mambas), foram extraídas algumas proteínas de 7 a 8 KDa com atividade seletiva a subtipos de receptores colinérgicos muscarínicos, as "toxinas muscarínicas". O hipocampo é uma das estruturas cerebrais onde a neurotransmissão colinérgica é importante e que, sabidamente, está envolvido na aquisição e consolidação da memória. Neste trabalho administramos MTx1 (2 ug/lado), MTx2 (0,74 ug/lado), MTx3 1,18 ou 2 ug/lado), ou o veículo (TFS) bilateralmente no hipocampo dorsal visando examinar os efeitos destas toxinas sobre a memória de ratas na tarefa comportamental de esquiva inibitória (EI). Foram utilizadas 81 ratas adultas, canuladas bilateralmente, e, após recuperação, treinadas na caixa de EI com choque de 0,5 mA (medida da latência de descida da plataforma); 24 h mais tarde, foram testadas na mesma caixa, sem choque, com teto de 300s de espera. Os animais tratados com MTx2 exibiram latências de descida no teste maiores que o grupo controle (veículo), um claro efeito facilitatório. Já MTx3 foi amnésico (latência do teste igual à do treino), mas apenas na dose mais alta. MTx1 não produziu nenhum efeito significativo. O efeito facilitatório já havia sido descrito por um dos autores (Jerusalinsky et al., 1993, Eur. J. Pharmac. 240:103-5). Como MTx1 e MTx2 são seletivas para o mesmo subtipo de receptor muscarínico (m1), embora com diferentes afinidades, esse efeito facilitatório precisa ser melhor estudado. Já a MTx3, mais seletiva para m4, aponta para distintos papéis dos diferentes subtipos de receptores muscarínicos no processamento da memória.

A consolidação da memória de longa duração requer a síntese de novas proteínas, o que ocorre em d... more A consolidação da memória de longa duração requer a síntese de novas proteínas, o que ocorre em dois períodos de tempo já definidos: imediatamente após o treino e 3-6 h após. Entretanto, ainda não estão claros os períodos em que ocorre a síntese de novo mRNA. Assim, nosso objetivo é estudar o efeito de dois inibidores da transcrição gênica sobre a retenção da tarefa de esquiva inibitória no rato. Ratos Wistar adultos machos foram submetidos à cirurgia estereotáxica para implantação de cânulas na região CA1 do hipocampo e foram treinados na tarefa de esquiva inibitória de uma via, sendo que receberam infusões bilaterais de α-amanitina, 5,6-dicloro-1-β-Dribofuranosilbenzimidazole (DRB) ou anisomicina 15 minutos antes ou imediatamente, 1, 2, 3, 4.5, 6, 7.5 ou 9 h após o treino. Tanto a α-amanitina quanto o DRB causaram déficit de memória de longa duração quando injetados 15 minutos antes do treino e imediatamente, 3, 4.5 e 6 h após o treino. Causaram também um déficit na memória de curta duração quando injetados 15 minutos antes do treino. A ação do inibidor da síntese proteica anisomicina foi similar, causando déficit de memória de longa duração se injetada 15 minutos antes ou 3-6 h após o treino. Esses achados nos levam a concluir que há dois períodos em que é necessária a síntese de mRNA para a consolidação da memória na tarefa de esquiva inibitória no rato: um próximo ao treino e outro 3-6 h após. E sugerem que o efeito amnésico da anisomicina pode depender em parte da síntese desse novo mRNA. (PIBIC-CNPq/UFRGS).