Impact of stress on inhibitory neuronal circuits, our tribute to Bruce McEwen

This manuscript is dedicated to the memory of Bruce S. McEwen, to commemorate the impact he had on how we understand stress and neuronal plasticity, and the profound influence he exerted on our scientific careers. The focus of this review is the impact of stressors on inhibitory circuits, particularly those of the limbic system, but we also consider other regions affected by these adverse experiences. We revise the effects of acute and chronic stress during different stages of development and lifespan, taking into account the influence of the sex of the animals. We review first the influence of stress on the physiology of inhibitory neurons and on the expression of molecules related directly to GABAergic neurotransmission, and then focus on specific interneuron subpopulations, particularly on parvalbumin and somatostatin expressing cells. Then we analyze the effects of stress on molecules and structures related to the plasticity of inhibitory neurons: the polysialylated form of the neural cell adhesion molecule and perineuronal nets. Finally, we review the potential of antidepressants or environmental manipulations to revert the effects of stress on inhibitory circuits

Chronic Stress Modulates Interneuronal Plasticity: Effects on PSA-NCAM and Perineuronal Nets in Cortical and Extracortical Regions

Chronic stress has an important impact on the adult brain. However, most of the knowledge on its effects is focused on principal neurons and less on inhibitory neurons. Consequently, recent reports have begun to describe stress-induced alterations in the structure, connectivity and neurochemistry of interneurons. Some of these changes appear to be mediated by certain molecules particularly associated to interneurons, such as the polysialylated form of the neural cell adhesion molecule (PSA-NCAM) and components of the perineuronal nets (PNN), specialized regions of the extracellular matrix. These plasticity-related molecules modulate interneuronal structure and connectivity, particularly of parvalbumin expressing basket interneurons, both during development and adult life. These inhibitory neurons are specially affected after chronic stress and in some stress-related disorders, in which the expression of PSA-NCAM and certain components of PNN are also altered. For these reasons we have decided to study PSA-NCAM, PNN and parvalbumin expressing interneurons after 10 days of chronic restraint stress, a time point in which its behavioral consequences are starting to appear. We have focused initially on the medial prefrontal cortex (mPFC), basolateral amygdala (BLA) and hippocampus, regions affected by stress and stress-related psychiatric diseases, but we have also explored the habenula and the thalamic reticular nucleus (TRN) due to the important presence of PNN and their relationship with certain disorders. PSA-NCAM expression was increased by stress in the stratum lacunosum-moleculare of CA1. Increases in parvalbumin immunoreactive cells were detected in the mPFC and the BLA, but were not accompanied by increases in the number of parvalbumin expressing perisomatic puncta on the somata of principal neurons. The number of PNN was also increased in the mPFC and the habenula, although habenular PNN were not associated to parvalbumin cells. Increased expression of parvalbumin and components of PNN were also detected in the TRN after chronic restraint stress, revealing for the first time substantial effects on this region. Our study shows that, even a short chronic stress protocol, can induce consistent changes in interneuronal plasticity-related molecules in cortical and extracortical regions, which may represent initial responses of inhibitory circuits to counteract the effects of this aversive experience

Análise do potencial antioxidante do composto dimetil-1-fenil-3,4-bis(fenilselenil)-1h-pirrol in vitro

O selênio é um micronutriente essencial para a saúde humana, uma vez que, entre outras funções, é um constituinte integral de selenoproteínas, as quais tem papel fundamental na manutenção do estado redox do organismo. Compostos orgânicos contendo selênio se mostram promissoras moléculas para estudos farmacológicos. Nesse sentido, investigamos compostos orgânicos de selênio que apresentam atividade biológica frente a distúrbios neuropsiquiátricos, como a depressão maior, que está associada, a um quadro de desequilíbrio oxidativo

3-(4-clorofenilselanil)-1-metil-1h-indol reverte o déficit cognitivo em camundongos submetidos ao modelo de privação do sono

O 3-(4-clorofenilselanil)-1-metil-1H-indol (CMI) é um composto orgânico de selênio que possui diversos efeitos farmacológicos, como o efeito do tipo antidepressivo em diferentes modelos animais, ansiolítico e anticâncer. Entre seus efeitos, porém, não foram caracterizadas suas propriedades em reverter o déficit cognitivo após períodos de privação do sono. A privação do sono está muito presente na vida de estudantes, trabalhadores e idosos e a irregularidade no ciclo circadiano afeta a fisiologia, sinapses e ativa o sistema nervoso simpático, o que aumenta a quantidade de cortisol (corticosterona em camundongos). O cortisol é o hormônio do estresse e é responsável por acelerar o metabolismo e tem um importante papel no declínio da memória e cognição que, por sua vez, são fundamentais para priorizar instintos de sobrevivência. A curto prazo, o declínio cognitivo possui a perda dessas funções, e ao longo prazo pode até causar causar dependência de um indivíduo a outro, como é encontrado em outras doenças neurológicas que apresentam demência, como Alzheimer. Com os dados acima descritos e sabendo que a privação do sono está se tornando um problema ainda mais emergente nos dias atuais, o que pode aumentar o déficit cognitivo da população, o objetivo deste trabalho foi descrever as propriedades do CMI em reverter o déficit cognitivo em camundongos submetidos a privação do sono

Bis(phenylimidazoselenazolyl) diselenide as an antioxidant compound: An in vitro and in vivo study

AbstractThe organoselenium compounds have been reported for many biological properties, especially as potent antioxidants. The compound bis(phenylimidazoselenazolyl) diselenide (BPIS) is a novel diaryl diselenide derivative, which shows antinociceptive and anti-inflammatory properties in mice, but whose antioxidant activity has not been studied. The present study aimed to investigate the antioxidant and toxicological potential of BPIS in brain of rats in vitro, and the effect of BPIS against the oxidative damage induced by sodium nitroprusside (SNP) in mouse brain. BPIS, at low molecular range, reduced lipid peroxidation (LP) and protein carbonyl (PC) content in rat brain homogenates (IC50 values of 1.35 and 0.74μM, respectively). BPIS also presented dehydroascorbate reductase-like and glutathione-S-transferase-like, as well as DPPH and NO-scavenging activities. Related to togicological assays, BPIS inhibited δ-ALA-D and Na+, K+-ATPase activities in rat brain homogenates and [3H]glutamate uptake in synaptosomes in vitro, but these effects were observed at higher concentrations than it had antioxidant effect (IC50 values of 16.41, 26.44 and 3.29μM, respectively). In vivo, brains of mice treated with SNP (0.335μmol per site; i.c.v.) showed an increase in LP and PC and a reduction in non protein thiol content, however, it was not observed significant alterations in antioxidant enzyme activities. BPIS (10mg/kg; p.o.) protected against these alterations caused by SNP. In conclusion, the results demonstrated the antioxidant action of BPIS in in vitro assays. Furthermore, BPIS protected against oxidative damage caused by SNP in mouse brain, strengthening the potential antioxidant effect of this compound

Impact of stress on inhibitory neuronal circuits, our tribute to Bruce McEwen

This manuscript is dedicated to the memory of Bruce S. McEwen, to commemorate the impact he had on how we understand stress and neuronal plasticity, and the profound influence he exerted on our scientific careers. The focus of this review is the impact of stressors on inhibitory circuits, particularly those of the limbic system, but we also consider other regions affected by these adverse experiences. We revise the effects of acute and chronic stress during different stages of development and lifespan, taking into account the influence of the sex of the animals. We review first the influence of stress on the physiology of inhibitory neurons and on the expression of molecules related directly to GABAergic neurotransmission, and then focus on specific interneuron subpopulations, particularly on parvalbumin and somatostatin expressing cells. Then we analyze the effects of stress on molecules and structures related to the plasticity of inhibitory neurons: the polysialylated form of the neural cell adhesion molecule and perineuronal nets. Finally, we review the potential of antidepressants or environmental manipulations to revert the effects of stress on inhibitory circuits