RESUMO
The role of physical exercise as a neuroprotective agent against ischemic injury has been extensively discussed. Nevertheless, the mechanisms underlying the effects of physical exercise on cerebral ischemia remain poorly understood. Here, we investigate the hypothesis that physical exercise increases ischemic tolerance by decreasing the induction of cellular apoptosis and glutamate release. Rats (n = 50) were submitted to a swimming exercise protocol for 8 weeks. Hippocampal slices were then submitted to oxygen and glucose deprivation. Cellular viability, pro-apoptotic markers (Caspase 8, Caspase 9, Caspase 3, and apoptosis-inducing factor), and glutamate release were analyzed. The percentage of cell death, the amount of glutamate release, and the expression of the apoptotic markers were all decreased in the exercise group when compared to the sedentary group after oxygen and glucose deprivation. Our results suggest that physical exercise protects hippocampal slices from the effects of oxygen and glucose deprivation, probably by a mechanism involving both the decrease of glutamatergic excitotoxicity and apoptosis induction.
Assuntos
Fator de Indução de Apoptose/metabolismo , Caspases/metabolismo , Ácido Glutâmico/metabolismo , Hipocampo/metabolismo , Condicionamento Físico Animal/fisiologia , Animais , Proteínas Reguladoras de Apoptose/metabolismo , Peso Corporal/fisiologia , Hipóxia Celular/fisiologia , Sobrevivência Celular/fisiologia , Masculino , Técnicas de Cultura de Órgãos , Condicionamento Físico Animal/métodos , Ratos , Ratos WistarRESUMO
Huntington's disease (HD) is a neurodegenerative disease characterized by prominent loss of neurons in the striatum and cortex. Traditionally research in HD has focused on brain changes as they cause progressive motor dysfunction, cognitive decline and psychiatric disorders. The discovery that huntingtin protein (HTT) and its mutated form (mHTT) are expressed not only in the brain but also in different organs and tissues paved the way for the hypothesis that HD might affect regions beyond the central nervous system (CNS). Besides pathological deposition of mHTT, other mechanisms, including inflammation, seem to underlie HD pathogenesis and progression. Altered inflammation can be evidenced even before the onset of classical symptoms of HD. Herein, we will discuss current pre-clinical and clinical evidence on immune/inflammatory changes in peripheral organs during HD development and progression. The understanding of the impact of inflammation on peripheral organs may open new venues for the development of novel therapeutic targets in HD.