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O envelhecimento é um processo acompanhado por uma série de mudanças físicas, fisiológicas e psicológicas, além de ser caracterizado pelo declínio de diferentes funções motoras e cognitivas, que afetam a independência do idoso. Particularmente na mulher, um acompanhante inevitável do envelhecimento é a menopausa. Desse modo, é natural o interesse em medidas terapêuticas que possam ser utilizadas para minimizar os sintomas da menopausa, bem como o prejuízo motor e cognitivo. Assim, o presente estudo teve como objetivo (i) avaliar o efeito da idade nos aspectos comportamentais, neuroquímicos e de ácidos graxos poli-insaturados em ratas jovens (3 meses de idade), de meia-idade (12 meses de idade) e senescentes (18 meses de idade); e, (ii) avaliar os efeitos da administração prolongada (90 dias) de diferentes doses (50, 100 e 200 mg/kg/dia) de isoflavonas (ISOs) no perfil comportamental, na análise bioquímica sérica e de estradiol, na quantificação dos níveis de neurotransmissores encefálicos e achados anatomopatológicos em ratas de meia-idade. Os resultados da primeira etapa mostraram que: ratas com 12 e 18 meses de idade apresentaram: 1) diminuição da frequência de levantar e de grooming no campo aberto; 2) aumento do comportamento tipo-ansioso no labirinto em cruz elevado e na caixa claro-escuro; 3) prejuízo na memória espacial observada no labirinto de Barnes; 4) diminuição, sobretudo, nos níveis de dopamina e de seus metabólitos no córtex pré-frontal (CPF), no hipotálamo, no hipocampo e no estriado; 5) diminuição dos níveis dos hidróxidos 12 e 15/14 do ácido araquidônico (AA) no CPF de ratas com 18 meses de idade. Esses dados em conjunto evidenciam prejuízo motor e cognitivo, aumento do comportamento tipo-ansioso, bem como redução nos níveis de monoaminas e dos hidróxidos do AA com o avanço da idade das ratas. Em relação ao tratamento prolongado com diferentes doses de ISOs em ratas de meia-idade, os resultados mostraram que: 1) não houve alterações motoras e no comportamento tipo-ansioso; 2) evidenciou melhora no desempenho cognitivo espacial; 3) mostrou aumento nos níveis séricos de estradiol e 4) promoveu aumento nos níveis de glutamato e de GABA no CPF e no hipotálamo. Esses achados sugerem que o tratamento prolongado com diferentes doses de ISOs em ratas de meia-idade, foi capaz de melhorar a performance cognitiva espacial e esse efeito pode ser associado ao aumento dos níveis de estrógeno, bem como ao aumento dos níveis de glutamato e de GABA no córtex pré-frontal e no hipotálamo, evidenciando também um possível efeito neuroprotetor das ISOs em ambas regiões. / Aging is a process accompanied by a series of physical, physiological and psychological changes, besides being characterized by the decline of different motor and cognitive functions, which affect the independence of the elderly. Specifically, in women, an inevitable companion of aging is menopause. Therefore, it is of high interest therapeutic procedures that can be used to reduce the symptoms of menopause, as well as motor and cognitive impairment. Thus, the present study aimed to (i) evaluate the effect of age on behavioral, neurochemical and polyunsaturated fatty acids aspects in young (3 months old), middle-aged (12 months old) and senescent (18 months of age) female rats; and (ii) to evaluate the effects of prolonged (90 days) administration of different doses (50, 100 and 200 mg/kg/day) of isoflavones (ISOs) in the behavioral profile, biochemical and estradiol serum analysis, brain neurotransmitters levels and anatomopathological findings in middle-aged rats. Our first results showed that rats at 12 and 18 months of age: 1) presented a decrease in rearing and grooming frequency in the open field; 2) increase of anxiety-like behavior in the elevated plus maze and light-dark box; 3) spatial memory impairment observed in the Barnes maze; 4) a decrease mainly in the levels of dopamine and its metabolites in the prefrontal cortex (PFC), hypothalamus, hippocampus and striatum; 5) decreased levels of 12 and 15/14 arachidonic acid (AA) hydroxides in the PFC in 18-month old rats . These data altogether show motor and cognitive impairment, increase in anxiety-like behavior, as well as reductions in monoamine levels and AA hydroxides as the rat age progresses. Regarding the prolonged treatment with different doses of ISOs in middle-aged rats, the results showed that: 1) there were no motor or anxiety-like behavior alterations; 2) there was an improvement in spatial cognitive performance; 3) increase in serum estradiol levels and 4) increase in glutamate and GABA levels in the PFC and hypothalamus. These findings suggest that prolonged treatment with different doses of ISOs could improve spatial cognitive performance and that this effect may be associated with increased estrogen levels, as well as increased levels of glutamate and GABA in the prefrontal cortex and hypothalamus, evidencing a possible neuroprotective effect of ISOs in both regions.

INTRODUÇÃO: A isquemia cerebral é uma das principais causas de morte no Brasil, segundo levantamento da Sociedade Brasileira de Neurologia em 2000, sendo a terceira causa de morte após doenças cardiovasculares e o câncer, além de ser uma das maiores causas de sequela permanente capaz de gerar incapacidade. Nas últimas décadas, estudos experimentais tem demonstrado efeitos benéficos do exercício físico associado à isquemia cerebral. Vários mecanismos moleculares estão envolvidos na fisiopatologia da isquemia cerebral, entre eles as alterações nos perfis de expressão de neurotransmissores. Pesquisas atuais também destacam o papel dos microRNAs na isquemia cerebral quanto na regulação dos neurotransmissores. Portanto, analisar a expressão de neurotransmissores e microRNAs associados à isquemia cerebral, assim como o papel dos benefícios promovidos pelo exercício físico poderá contribuir na elucidação de possíveis vias moleculares com efeito neuroprotetor. MATERIAIS E MÉTODOS: Foram utilizados 48 animais divididos em quatro grupos experimentais: controle, submetido à isquemia cerebral, submetido ao exercício físico e submetido ao exercício físico associado à isquemia cerebral. A metodologia de PCR em tempo real foi utilizada para analisar a expressão dos miRNAs; miR15b, miR29b, miR-219 e miR-222. RESULTADOS E CONCLUSÃO: não observamos diferenças estatísticas significativas na expressão dos miRNAs miR-15b, miR- 12 29b, miR-219 e miR-222 no tecido cerebral dos grupos submetidos à isquemia cerebral, submetidos ao exercício físico e na associação dos dois grupos quando comparados ao grupo controle. Entretanto, os miRNAs miR-15b e miR222 apresentaram maior expressão no grupo com a associação da isquemia cerebral e exercício físico / INTRODUCTION: Cerebral ischemia is one of the main causes of death in Brazil, according to a survey by the Brazilian Society of Neurology in 2000, being the third cause of death after cardiovascular diseases and cancer, besides being one of the major causes of permanent sequela capable of generate disability. In the last decades, experimental studies have shown beneficial effects of physical exercise associated with cerebral ischemia. Several molecular mechanisms are involved in the pathophysiology of cerebral ischemia, including changes in neurotransmitter expression profiles. Current research also highlights the role of microRNAs both in the process of cerebral ischemia and in the regulation of neurotransmitters. Therefore, analyzing the expression of neurotransmitters and microRNAs associated with cerebral ischemia, as well as the role of the benefits promoted by physical exercise may contribute to the elucidation of possible molecular pathways with neuroprotective effect. MATERIALS AND METHODS: 48 animals were divided into 4 experimental groups: control, cerebral ischemia, physical exercise and physical exercise associated with cerebral ischemia. The real-time PCR methodology was used to analyze miRNA expression: miR15b, miR-29b, miR219 and miR-222. RESULTS AND CONCLUSION: We did not observe statistically significant differences in the miRNA expression of miRNAs: miR 15b, miR-29b, miR-219 and miR-222 in brain tissue groups submitted to 15 cerebral ischemia, physical exercise and in the association of the two groups when compared to the group control. However, the miR-15b and miR-222 levels of expression increased in the group of cerebral ischemia associated with physical exercise

New neurons are continuously generated in the olfactory system of adult mice, including olfactory sensory neurons (OSNs) in the olfactory epithelium (OE) and interneurons, produced in the subventricular zone (SVZ) and migrated toward olfactory bulb (OB) along rostral migratory stream (RMS). The present study observed the effects of target neuron loss on the life-span and maturation of adult-born OSNs in the OE and on the proliferation, migration and differentiation of SVZ stem cells in the forebrain after eliminating bulb neurons. We found the life-span of newborn neurons in the absence of synaptic targets was shortened, but the timing of maturation was not delayed. In addition, SVZ cells continued to divide and migrate to the damaged bulb, and the migration of newborn cells in the RMS on the contralateral side was delayed at 2 weeks post-BrdU. Also, the proliferation of cells in dentate gyrus of the hippocampus was not affected by OB damage at 3 weeks post-lesion, though lesion affects occurred in the adult SVZ/RMS. / by Huan Liu. / Thesis (M.S.)--Florida Atlantic University, 2008. / Includes bibliography. / Electronic reproduction. Boca Raton, Fla., 2008. Mode of access: World Wide Web.

Serotonin syndrome (SS) is a drug-induced toxicity caused by an excess of serotonin (5-HT) in the central nervous system (CNS). The symptoms of the disorder range from mild to severe, with the severe state evoking life-threatening hyperthermia. Autonomic dysfunction is controlled in part by serotonin receptors, with the 5-HT2A receptor responsible for increasing core body temperature (Tcor). Our results show that the 5-HT2A receptors on the preoptic/anterior hypothalamus (PO/AH) and prefrontal cortex (PFC), in particular, are sensitive to changes in ambient temperature (Tamb). The toxic increase of 5-HT is postulated to occur due to the temperature-dependent activation of these receptors that promotes a positive feedback mechanism. Our results suggest that changes in Tamb can either exacerbate or alleviate the symptom and that this is mediated by the 5-HT2A receptors. Understanding the mechanism involved in elevating Tcor is imperative in treating and preventing the disorder. / by Swapna Krishnamoorthy. / Vita. / Thesis (M.S.)--Florida Atlantic University, 2008. / Includes bibliography. / Electronic reproduction. Boca Raton, Fla., 2008. Mode of access: World Wide Web.

The rodent hippocampus is critical for processing spatial memory but its contribution to non-spatial, specifically object memory is debated. The cognitive map theory of hippocampal function states that the hippocampus stores relationships of goal locations (places) to discrete items (objects) encountered within environments. Dorsal CA1 place cells were recorded in male C57BL/6J mice performing three variations of the novel object recognition paradigm to define "object-in-context" representation of hippocampal neuronal activity that may support object memory. Results indicate, (i) that place field stability is higher when polarizing environmental cues are provided during object recognition; (ii) hippocampal place fields remain stable throughout the novel object recognition testing without a polarizing cue; and (iii) time dependent effects on stability when objects were dissociated from the context. These data indirectly support that the rodent hippocampus processes object memory, and challenge the view that "object-in-context" representations are formed when mice perform novel object recognition task. / by Herborg Nanna âAsgeirsdâottir. / Thesis (M.A.)--Florida Atlantic University, 2013. / Includes bibliography. / Mode of access: World Wide Web. / System requirements: Adobe Reader.

SK channels are small conductance Ca2+-activated K+ channels expressed throughout the CNS. SK channels modulate the excitability of hippocampal CA1 neurons by affecting afterhyperpolarization and shaping excitatory postsynaptic responses. Such SK-mediated effects on activity-dependent neuronal excitability and synaptic strength are thought to underlie the modulatory influence of SK channels on memory encoding. Here,the effect of a new SK1 selective activator, GW542573X, on hippocampal-dependent object memory, contextual and cued conditioning, and trace fear conditioning was examined. The results demonstrated that pre- but not post-training systemic administration of GW542573X impaired object memory and trace fear memory in mice 24 h after training. Contextual and cued fear memory were not disrupted. These current data suggest that activation of SK1 subtype-containing SK channels impairs long-term memory. These results are consistent with converging evidence that SK channel activation suppressed behaviorally triggered synaptic plasticity necessary for encoding hippocampal-dependent memory. / Includes bibliography. / Thesis (M.S.)--Florida Atlantic University, 2015. / FAU Electronic Theses and Dissertations Collection