Aquisicão do comportamento de esquiva no labirinto em cruz elevado: efeito de um inibidor da síntese de óxido nítrico

Dissertação (mestrado) - Universidade Federal de Santa Catarina, Centro de Ciências Biológicas. Programa de Pós-Graduação em Neurociências.Avaliação do comportamento de esquiva de ratos em diferentes configurações do Labirinto em Cruz Elevado (LCE) e verificação do efeito do Nw-nitro-L-Arginina metil éster ou L-NAME sobre a aquisição desta esquiva. O experimento 1 verificou a influência do grau de luminosidade sobre a esquiva de ratos no LCE; utilizaram-se três configurações do modelo com dimensões idênticas e com diferentes materiais de confecção dos braços fechados (vidro transparente, vidro fumê e madeira), sendo 3 grupos (LCEVidro, LCEFumê e LCEMadeira). O experimento 2 verificou o papel do L-NAME sobre a aquisição da esquiva dos braços abertos (BA) no LCE. Quatro grupos de animais foram expostos por duas vezes ao LCEFumê: grupo salina (sal 0,9) e grupos L-NAME (5, 10 e 50 mg/kg). As variáveis consideradas foram % e número de entradas nos BA (%A e A, respectivamente), % de tempo de permanência nestes braços (%T) e número de entradas nos braços fechados (F); também foram analisadas variáveis etológicas. Ocorreu aprendizagem de esquiva dos BA nos três tipos de LCE, sugerindo que o nível de luminosidade não é uma variável relevante no processo de aquisição da esquiva ao longo da primeira exposição (E1); elevada esquiva também foi observada, comparando-se a segunda exposição (E2) com E1. Porém, o grupo LCEVidro apresentou elevada exploração dos BA na E1 e prejuízo na aquisição de esquiva, caracterizando baixo nível de medo, o que pode prejudicar a detecção do efeito de drogas ansiolíticas. O experimento 2 mostrou que o grupo de animais tratado com L-NAME (50 mg/kg) exibiu prejuízo na aquisição da esquiva, caracterizado por maior exploração BA na E2, em relação ao grupo controle; o mesmo grupo não exibiu aumento da esquiva ao longo da E1. Os resultados do experimento 2 indicaram que o óxido nítrico parece mediar o processo de aprendizagem de esquiva dos BA no LCE

Coumestrol has neuroprotective effects before and after global cerebral ischemia in female rats

AbstractGlobal ischemia arising during cardiac arrest or cardiac surgery causes highly selective, delayed death of hippocampal CA1 neurons. Phytoestrogens are naturally occurring plant-derived compounds that are present in the human diet and are considered selective estrogen receptor (ER) modulators. The phytoestrogen coumestrol is a potent isoflavonoid, with binding affinities for both ER-α and ER-β that are comparable to those of 17b-estradiol. The present study examined the hypothesis that coumestrol protects hippocampal neurons in ovariectomized rats in a model of cerebral global ischemia. Ovariectomized rats were subjected to global ischemia (10min) or sham surgery and received a single intracerebroventricular or peripheral infusion of 20μg of coumestrol, 20μg of estradiol or vehicle 1h before ischemia or 0h, 3h, 6h or 24h after reperfusion. Estradiol and coumestrol afforded significant neuroprotection in all times of administration, with the exception of estradiol given 24h after the ischemic insult. Animals received icv infusion of the broad-spectrum ER antagonist ICI 182,780 (50μg) or vehicle into the lateral ventricle just before the E2 or coumestrol administration. The ER antagonist abolished estradiol protection, consistent with a role of classical ERs. In contrast, ICI 182,780 effected only partial reversal of the neuroprotective actions of coumestrol, suggesting that other cellular mediators in addition to classical ERs may be important. Additional research is needed to determine the molecular targets mediating the neuroprotective action of coumestrol and the therapeutic potential of this phytoestrogen in the mature nervous system

O enriquecimento ambiental contínuo em ratos neonatos não reverte déficit mnemônico causado pela hipóxia-isquemia neonatal

09

Comparative overview of the effects of aerobic and resistance exercise on anxiety-like behavior, cognitive flexibility, and hippocampal synaptic plasticity parameters in healthy rats

Clinical studies show that physical exercise has anxiolytic and pro-cognitive properties for both healthy individuals and psychiatric patients. Most of these data refer to the effects of aerobic exercise. However, other modalities such as resistance exercise deserve more attention because they may also modulate brain function. This study aimed to compare the effects of an aerobic exercise protocol on a treadmill and a resistance exercise protocol on a ladder apparatus on anxiety-like behavior, cognitive flexibility, and neuroplasticity parameters in healthy animals. Adult male Wistar rats were divided into three groups: sedentary control, aerobic training, and resistance training. Subsequently, they were evaluated in the elevated plus-maze (EPM), light-dark box, and modified hole board (mHB) tests. The expressions of synaptophysin and postsynaptic plasticity protein 95 in the dorsal and ventral hippocampus were analyzed by immunofluorescence. The results demonstrated an anxiolytic effect promoted by exercise in the EPM, particularly in the animals submitted to aerobic training, and a mild pro-learning effect of both exercise modalities was observed in the mHB test. All groups showed similar outcomes in the other evaluations. Therefore, the exercise modalities investigated in the present study did not provide considerable modifications to such aspects of the emotional/cognitive functions and neuroplasticity under physiological contexts. Perhaps the two types of exercise acted in neurobiological pathways not analyzed in this study, or the effects may emerge under pathological contexts. These hypotheses should be tested in future studies

The modified 2VO ischemia protocol causes cognitive impairment similar to that induced by the standard method, but with a better survival rate

Permanent bilateral occlusion of the common carotid arteries (2VO) in the rat has been established as a valid experimental model to investigate the effects of chronic cerebral hypoperfusion on cognitive function and neurodegenerative processes. Our aim was to compare the cognitive and morphological outcomes following the standard 2VO procedure, in which there is concomitant artery ligation, with those of a modified protocol, with a 1-week interval between artery occlusions to avoid an abrupt reduction of cerebral blood flow, as assessed by animal performance in the water maze and damage extension to the hippocampus and striatum. Male Wistar rats (N = 47) aged 3 months were subjected to chronic hypoperfusion by permanent bilateral ligation of the common carotid arteries using either the standard or the modified protocol, with the right carotid being the first to be occluded. Three months after the surgical procedure, rat performance in the water maze was assessed to investigate long-term effects on spatial learning and memory and their brains were processed in order to estimate hippocampal volume and striatal area. Both groups of hypoperfused rats showed deficits in reference (F(8,172) = 7.0951, P < 0.00001) and working spatial memory [2nd (F(2,44) = 7.6884, P < 0.001), 3rd (F(2,44) = 21.481, P < 0.00001) and 4th trials (F(2,44) = 28.620, P < 0.0001)]; however, no evidence of tissue atrophy was found in the brain structures studied. Despite similar behavioral and morphological outcomes, the rats submitted to the modified protocol showed a significant increase in survival rate, during the 3 months of the experiment (P < 0.02)