O ciclo da vesícula sináptica, espinhos dendríticos e a transdução de sinal

In the nervous system, the synapse is the structure that allows a neuron pass an electrical or chemicalsignal to another neuron or another cell (muscle or glandular). The word synapse comes from "synaptein"that Sir Charles Scott Sherrington and his colleagues minted from the Greek "syn" (together) and "haptein"(buckling). Most part of the synaptic transmission is performed through chemical synapses. Chemicalsynapses have a slower response than the electric ones; they have the advantage of amplifying thesignal generated through a cascade of second messengers. Chemical synapses can be excitatory orinhibitory and are characterized by a presynaptic terminal (where there are vesicles that contain theneurotransmitters) in contact with a postsynaptic terminal (where there are the ionotropic and metabotropicreceptors) separated by the synaptic cleft. Synapses can occur on axons (axo-axonal), on dendrites (axodendritic), on soma (axo-somatic) and on dendritic spines. Dendritic spines are small profusions withthe function of synaptic compartmentalization. There is much information about classic neurotransmitters,such as acetylcholine, glutamate, GABA, glycine, dopamine, norepinephrine, and serotonin, but the studyof new neurotransmitter (i. e., ATP, nitric oxide, endocannabinoids, and neuropeptides) has advancedenormously. This review is a collection summary of key information from the recent literature describingthe molecular and functional aspects of the cycle of synaptic vesicle, the composition of postsynapticdensity, dendritic spines, and signal transduction.No sistema nervoso, a sinapse é a estrutura que permite a um neurônio passar um sinal elétrico ouquímico a outro neurônio ou outra célula (muscular ou glandular). A palavra sinapse vem de "synaptein",palavra que Sir Charles Scott Sherrington e seus colegas acunharam do grego "syn" (junto) e "haptein"(afivelar). As sinapses podem ser separadas entre elétricas e químicas, porém a maior parte da transmissão sináptica é realizada através das sinapses químicas. Apesar das sinapses químicas teremuma resposta mais lenta que as elétricas, elas possuem a vantagem da amplificação do sinal geradaatravés de uma cascata de segundos mensageiros. As sinapses químicas podem ser excitatórias ouinibitórias e são caracterizadas por um terminal pré-sináptico (onde estão presentes as vesículas quecontêm os neurotransmissores) em contato com um terminal pós-sináptico (onde estão presentes osreceptores ionotrópicos e metabotrópicos para esses neurotransmissores) separados pela fenda sináptica. As sinapses típicas acontecem sobre axônios (axo-axônicas), sobre dendritos (axo-dendríticas), sobre o soma de outro neurônio (axo-somáticas) e sobre os espinhos dendríticos. Os espinhosdendríticos são pequenas profusões da membrana celular especializadas na compartimentalizaçãosináptica. Atualmente há muita informação sobre a biossíntese dos neurotransmissores clássicoscomo acetilcolina, glutamato, GABA, glicina, dopamina, noradrenalina e serotonina e os seus receptores específicos para o funcionamento do sistema nervoso central (SNC). Ao mesmo tempo o estudo denovas substâncias neurotransmissoras (por exemplo ATP, óxido nítrico, endocanabinóides e neuropeptídeos) tem avançado enormemente. Esta revisão é uma seleção resumida de informações fundamentais a partir da literatura mais recente dos principais aspectos funcionais e moleculares do ciclo davesícula sináptica, da composição da densidade pós-sináptica, dos espinhos dendríticos e do mecanismo de transdução de sinal

Neurotransmissão glutamatérgica e plasticidade sináptica: aspectos moleculares, clínicos e filogenéticos

Communication between neurons is subject to constant changes, even in the adult brain. This ability ofneural circuits to strengthen or weaken their specific synaptic interactions (a phenomenon known assynaptic plasticity) may occur according to different environmental demands, which favors the idea thatdynamic changes in the communication between neurons underlie behavioral flexibility (i.e., learningand memory processes). In recent decades, advances in neuroscience has allowed a better understanding of synaptic plasticity, specially the plasticity of glutamatergic synapses, whose molecular processes of synaptic change appear to be among the most common throughout the central nervous system.Much of this progress in basic science has contributed to a better understanding of pathological processes involving the glutamatergic synapses, such as Alzheimer's disease. Furthermore, the growingunderstanding about the physiology of glutamatergic communication has helped explain how synapses,in general, would have originated and evolved in the phylogenetic scale of the Metazoa. This reviewattempts to address clinical aspects of glutamatergic neurotransmission, coA comunicação entre neurônios é passível de constantes modificações, até mesmo no encéfalo adulto.Esta capacidade de circuitos neuronais fortalecerem ou enfraquecerem suas interações sinápticasespecíficas (fenômeno conhecido como plasticidade sináptica) pode ocorrer de acordo com as diferentes demandas ambientais, o que favorece a noção de que alterações dinâmicas na comunicação entreneurônios estão na base da flexibilidade comportamental (i.e., processos de aprendizagem e memó-ria). Nas últimas décadas, o avanço das neurociências tem permitido uma melhor compreensão arespeito da plasticidade sináptica, especialmente a plasticidade de sinapses glutamatérgicas, cujosprocessos moleculares de modificação sináptica parecem estar entre os mais comuns de todo osistema nervoso central. Boa parte desse progresso na ciência básica tem contribuído para uma melhor compreensão acerca dos processos patológicos envolvendo as sinapses glutamatérgicas, comoa doença de Alzheimer. Além disso, a crescente compreensão sobre o funcionamento da comunicaçãoglutamatérgica tem ajudado a esclarecer como as sinapses, em geral, teriam se originado e evoluídona escala filogenética do reino animal (Metazoa). A presente revisão procura abordar aspectos clínicosda neurotransmissão glutamatérgica, porém propondo uma contextualização de tais aspectos clínicosem relação a conhecimentos básicos sobre plasticidade sináptica e evolução das sinapses

Role of 5-HT1A Receptor in Vilazodone-Mediated Suppression of L-DOPA-Induced Dyskinesia and Increased Responsiveness to Cortical Input in Striatal Medium Spiny Neurons in an Animal Model of Parkinson’s Disease

L-DOPA therapy in Parkinson’s disease (PD) is limited due to emerging L-DOPA-induced dyskinesia. Research has identified abnormal dopamine release from serotonergic (5-HT) terminals contributing to this dyskinesia. Selective serotonin reuptake inhibitors (SSRIs) or 5-HT receptor (5-HTr) agonists can regulate 5-HT activity and attenuate dyskinesia, but they often also produce a loss of the antiparkinsonian efficacy of L-DOPA. We investigated vilazodone, a novel multimodal 5-HT agent with SSRI and 5-HTr1A partial agonist properties, for its potential to reduce dyskinesia without interfering with the prokinetic effects of L-DOPA, and underlying mechanisms. We assessed vilazodone effects on L-DOPA-induced dyskinesia (abnormal involuntary movements, AIMs) and aberrant responsiveness to corticostriatal drive in striatal medium spiny neurons (MSNs) measured with in vivo single-unit extracellular recordings, in the 6-OHDA rat model of PD. Vilazodone (10 mg/kg) suppressed all subtypes (axial, limb, orolingual) of AIMs induced by L-DOPA (5 mg/kg) and the increase in MSN responsiveness to cortical stimulation (shorter spike onset latency). Both the antidyskinetic effects and reversal in MSN excitability by vilazodone were inhibited by the 5-HTr1A antagonist WAY-100635, demonstrating a critical role for 5-HTr1A in these vilazodone actions. Our results indicate that vilazodone may serve as an adjunct therapeutic for reducing dyskinesia in patients with PD

The Psychological Impact of the COVID-19 Pandemic in Remote Learning in Higher Education

Stressful events can cause a significant impact on education; however, it is not yet clear how the interplay between anxiety, work, and social dysfunction relates to learning impairments. In this study, we investigated the impact of the COVID-19 pandemic on students’ learning and mental health. This study was conducted during four modules of a remote Psychopharmacology course between 5 October and 20 December 2020. We collected data from 28 Psychology undergraduate students at the University of São Paulo, Brazil. We used pre- and post-test multiple-choice questions to obtain a quantitative measure of learning. Students completed an online survey to report demographic information, functional impairment (Work and Social Adjustment scale; WSAS), generalized anxiety (Generalized Anxiety Disorder scale; GAD-7), coronavirus anxiety (Brazilian adapted version of the Coronavirus Anxiety Scale; CAS-BR), and self-perception with the remote lectures’ methodology. In our sample, 42.9% of respondents experienced symptoms of generalized anxiety disorders (GAD-7 ≥ 15), and 53.6% had moderate to severe functional impairment (WSAS > 20). We also observed an overlapping profile of highly anxious and dysfunctional students. A chi-square test of independence revealed a relation between pairs of multiple-choice questions answers and GAD-7 scores, indicating that less anxious students were more likely to perform better in pairs of pre- and post-tests. Intriguingly, the correlational analysis suggested that students with moderate to severe functional impairment (WSAS scores > 20) were less likely to change from an incorrect to a correct answer to pairs of pre- and post-tests. This data suggests that psychological distress and anxiety states might influence students’ ability to coordinate social and work activities and performance during remote learning. Although this study evaluated a small sample of students, our data highlights the importance of investigating anxiety and functional impairment measures as part of the remote-learning curriculum