RESUMO
Preclinical and clinical studies demonstrate that stress may be implicated in the risk of neurodegenerative diseases such as Alzheimer's disease (AD). Our study aimed to investigate the effects of acute and chronic immobilization stress (IS) on the gene transcriptions of beta-actin, amyloid precursor protein (APP) and mitogen activated protein kinase-1 (MAPK-1), proteins related to synaptic plasticity and neuronal degeneration. Male Wistar rats were exposed to IS for five hours daily for 3 days (acute stress) or through 7-14-21 days (chronic stress). At the end of exposure periods, total RNA was purified from the cortex and hippocampus. The amounts of beta-actin, APP and MAPK-1 mRNA were determined with real time PCR method. Our results indicate that the mRNA expression of beta-actin and APP followed a U-shaped time-response curve. Both acute and chronic IS caused a significant increase in beta-actin and MAPK-1 mRNA expression. Significant APP mRNA elevation was observed only by the 3rd week after RS. Our findings demonstrate that both acute and chronic IS lead to gene transcriptional changes of beta-actin, APP and MAPK-1. These proteins maintain the normal function of the cytoskeleton and the synaptic plasticity. The above changes may lead to cognitive deterioration, and the development of AD.
Assuntos
Actinas/genética , Doença de Alzheimer/genética , Doença de Alzheimer/fisiopatologia , Precursor de Proteína beta-Amiloide/genética , Proteína Quinase 1 Ativada por Mitógeno/genética , Plasticidade Neuronal/genética , Estresse Psicológico/genética , Transcrição Gênica , Actinas/metabolismo , Doença Aguda , Doença de Alzheimer/psicologia , Precursor de Proteína beta-Amiloide/metabolismo , Animais , Doença Crônica , Imobilização , Masculino , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , RNA Mensageiro/genética , Ratos , Ratos Wistar , Reação em Cadeia da Polimerase em Tempo Real , Fatores de Risco , Estresse Psicológico/complicaçõesRESUMO
Stress is a relatively new and emerging risk factor for Alzheimer's disease (AD). Severe stress can alter brain characteristics such as neuronal plasticity, due to changes in the metabolism of cytoskeletal proteins. In this study, male Wistar rats were exposed to restraint stress (RS) for 5 h daily for different time periods. At the end of the exposure periods, the amounts of ß-actin, cofilin, amyloid precursor protein (APP) and mitogen-activated protein kinase 1 (MAPK-1) RNAs and proteins were investigated. The mRNA expressions of ß-actin, cofilin and MAPK-1 followed U-shaped time course. Acute (3 days) and chronic (21 days) RS caused a fourfold and tenfold increases, respectively, in hippocampal ß-actin mRNA expression. In the case of cofilin mRNA expression, elevations were detected in the hippocampus on days 3, 7 and 21. The APP mRNA level was increased on day 21. On protein level, chronic stress elevated the levels of ß-actin, cofilin and APP in the hippocampus. These results suggest that stress causes the induction of some genes and proteins that are also elevated in AD selectively in the hippocampal region of the rat brain.
