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

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

Distribution of glutamate receptors in the posterodorsal medial amygdala of adult male rats

The rat posterodorsal medial amygdala (MePD) has a remarkable neuronal plasticity and responds to olfactory/pheromonal stimuli to modulate emotional and reproductive behaviors. Glutamate is locally released by incoming sensorial pathways to establish and enforce synaptic inputs. Here, we combined DiI dye and immunolabeling procedure under confocal microscopy to describe the presence and distribution of glutamate receptors on neurons of the MePD of adult male rats. Western blot analysis interrogated binding specificity. Both AMPA (GluA1-4 subunits) and NMDA (GluN1 subunit) receptors were immunolabeled on cell bodies and along proximal and distal dendritic shafts. AMPA receptors were mainly observed on mushroom and stubby/wide spines, whereas NMDA receptors were found on thin spines. Colocalization of AMPA and NMDA receptors occurred in some spines. Filopodium did not show immunolabeled puncta on it. Our results are different from the distribution of glutamate receptors in the amygdaloid lateral nucleus, an upstream area involved with emotional processing, and suggest a region-specific excitatory transmission at proximal and distal dendritic branches. Altogether, these data provide new information for synaptic processing in the MePD likely related to the modulation of social behavior in rats

The "single-section" golgi method adapted for formalin-fixed human brain and light microscopy

The Golgi method has been used for over a century to describe the general morphology of neurons in the nervous system of different species. The ""single-section"" Golgi method of Gabbott and Somogyi (1984) and the modifications made by Izzo et al. (1987) are able to produce consistent results. Here, we describe procedures to show cortical and subcortical neurons of human brains immersed in formalin for months or even years. The tissue was sliced with a vibratome, post-fixed in a combination of paraformaldehyde and picric acid in phosphate buffer, followed by osmium tetroxide and potassium dicromate, ""sandwiched"" between cover slips, and immersed in silver nitrate. The whole procedure takes between 5 and 11 days to achieve good results. The Golgi method has its characteristic pitfalls but, with this procedure, neurons and glia appear well-impregnated, allowing qualitative and quantitative studies under light microscopy. This contribution adds to the basic techniques for the study of human nervous tissue with the same advantages described for the ""single-section"" Golgi method in other species; it is easy and fast, requires minimal equipment, and provides consistent results. (C) 2010 Elsevier B.V. All rights reserved

Dendritic spines of the medial amygdala: plasticity, density, shape, and subcellular modulation by sex steroids

The medial nucleus of the amygdala (MeA) is a complex component of the “extended amygdala” in rats. Its posterodorsal subnucleus (MePD) has a remarkable expression of gonadal hormone receptors, is sexually dimorphic or affected by sex steroids, and modulates various social behaviors. Dendritic spines show remarkable changes relevant for synaptic strength and plasticity. Adult males have more spines than females, the density of dendritic spines changes in the course of hours to a few days and is lower in proestrous and estrous phases of the ovarian cycle, or is affected by both sex steroid withdrawal and hormonal replacement therapy in the MePD. Males also have more thin spines than mushroom-like or stubby/wide ones. The presence of dendritic fillopodia and axonal protusions in the MePD neuropil of adult animals reinforces the evidence for local plasticity. Estrogen affects synaptic and cellular growth and neuroprotection in the MeA by regulating the activity of the cyclic AMP response element-binding protein (CREB)-related gene products, brain-derived neurotrophic factor (BDNF), the anti-apoptotic protein B-cell lymphoma-2 (Bcl-2) and the activity-regulated cytoskeleton-related protein (Arc). These effects on signal transduction cascades can also lead to local protein synthesis and/or rearrangement of the cytoskeleton and subsequent numerical/morphological alterations in dendritic spines. Various working hypotheses are raised from these experimental data and reveal the MePD as a relevant region to study the effects of sex steroids in the rat brai

Plasma hormonal profiles and dendritic spine density and morphology in the hippocampal CA1 stratum radiatum, evidenced by light microscopy, of virgin and postpartum female rats

Successful reproduction requires that changes in plasma follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), oxytocin (OT), estrogen (E2) and progesterone (P4) occur together with the display of maternal behaviors. Ovarian steroids and environmental stimuli can affect the dendritic spines in the rat hippocampus. Here, studying Wistar rats, it is described: (a) the sequential and concomitant changes in the hormonal profile of females at postpartum days (PP) 4, 8, 12, 16, 20 and 24, comparing to estrous cycle referential values; (b) the dendritic spine density in the stratum radiatum of CA1 (CA1-SR) Golgi-impregnated neurons in virgin females across the estrous cycle and in multiparous age-matched ones; and (c) the proportion of different types of spines in the CA1-SR of virgin and postpartum females, both in diestrus. Plasma levels of gonadotrophins and ovarian hormones remained low along PP while LH increased and PRL decreased near the end of the lactating period. The lowest dendritic spine density was found in virgin females in estrus when compared to diestrus and proestrus phases or to postpartum females in diestrus (p 0.4). There were no differences in the proportions of the different spine types in nulliparous and postpartum females (p > 0.2). Results suggest that medium layer CA1-SR spines undergo rapid modifications in Wistar females across the estrous cycle (not quite comparable to Sprague–Dawley data or to hormonal substitutive therapy following ovariectomy), but persistent effects of motherhood on dendritic spine density and morphology were not found in this area