Alterations in expression of alpha1-adrenergic receptors possibly are involved in prevention of age-associated apoptosis in rat hippocampus by treadmill exercise

Abstract

OBJECTIVES: Exercise is assumed to attenuate age-related neuronal apoptosis, but the detailed mechanism(s) is not fully understood. alpha1-Adrenergic receptors (ARs) can either trigger or suppress apoptosis, therefore, here we determined the impact of treadmill exercise on the expression of the apoptosis regulatory proteins as well as alpha1-AR subtypes alpha1A- and alpha1B-ARs, in order to elucidate a possible association between apoptosis and the hippocampal expression of alpha1-ARs in aged male rats. METHODS: Twenty-one male Wistar rats were divided into 3 groups (n=7): young control, aged sedentary, and aged + exercise. Western blot for alpha1A- and alpha1B-ARs as well as pro-(Bax and p53) and anti-apoptotic (Bcl2) proteins was conducted. An 8-week regular moderate-intensity treadmill exercise intervention was carried out in exercise group. RESULTS: In aged rats, alpha1A-AR expression in the hippocampus was significantly increased, and exercise markedly prevented this event. While alpha1B-AR expression was no altered with aging, a marked reduction in alpha1B-AR level was detected in exercise group when compared to aged group. Furthermore, pro-apoptotic protein levels of Bax and p53 were upregulated and anti-apoptotic protein Bcl2 was downregulated in the aging hippocampus, but could be reversed by treadmill exercise. In the present research, exercise-induced reduction in alpha1A- and alpha1B-ARs was associated with an obvious downregulation of Bax/Bcl2 ratio in aged rats, suggesting that exercise may inhibit apoptosis through regulating alpha1-ARs, particularly alpha1A-AR. CONCLUSIONS: Our study suggests that manipulations attenuating alpha1-AR activity, including nonselective alpha1-adrenergic antagonists, may protect against hippocampal neurodegeneration in aging brains.