Sinalização e homeostase do cálcio hipocampal moduladas pelo exercício físico: implicações nos processos de memória e neuroproteção

• Ano de defesa: 2011
• Autor(a) principal: Luciana Estefani Drumond Carvalho
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de Minas Gerais; UFMG
• Palavras-chave em Português: Neuroproteção; Cálcio; Exercício; Glutamato; Memória; Mitocôndria; Farmacologia; Fisiologia
• Link de acesso: http://hdl.handle.net/1843/ICBD-8QCJP8

Calcium is the most versatile and important intracellular messenger in neurons, regulating a variety of neuronal processes, such as memory and cell death. This role in signaling has to be conducted against rigid homeostatic mechanisms. In this context, there is evidence supporting the fact that regular exercise has beneficial effects on the brain, which activate cellular and molecular pathways that contribute to memory and neuroprotection. Thus, the purpose of this study was to evaluate the modulation of calcium signaling and calcium homeostasis in memory and neuroprotection induced by exercise. Male Wistar rats were divided into two groups: exercise (EXE) and sedentary (SED). The EXE group was submitted to a swimming protocol 5x/week, 30 min/day for 4 weeks, with moderate training intensity (60% of maximum load). At the end of training period, animals were submitted to experimental protocols. Memory performance evaluated by displaced object preference tasks showed that spatial short-term memory was improved by swimming training. However, no effect was observed for the novel object task. We have used rat synaptosomes to study the effects of physical exercise on the release of glutamate and on the concentrations of free calcium ions inside the synaptosomes. The results indicate modifications of concentrations free Ca2+. Additionally, glutamate release was increased in the hippocampus of animals submitted to physical activity, with possible consequences for neurotransmission. Physical exercise was able to induce neuroprotection in hippocampal slices submitted to oxygen glucose deprivation, decreasing the number of cell death and increasing de viability in EXE , in addition to a reduced glutamate release in this group. The in vitro functional mitochondria experiments demonstrated that hippocampal mitochondria from EXE group required the same levels of Ca2+ than those from SED group to open the PTP. In addition, these assays showed that hippocampal mitochondrias from TRE group respond to the permeability pore transition (PPT) inhibitor, cyclosporine A (CsA) as efficiently as mitochondrias from SED group. Interestingly CypD expression in hippocampal mitochondria was slower in SED group. In summary, our results are in accordance with the literature regarding the beneficial and neuroprotective effects of exercise, pointing to pathways that increase the mechanisms involved in the calcium-independent and -dependent glutamate release. However, the calcium retention capacity (CRC) seems do not contribute to the observed neuroprotection.