Dehydroepiandrosterone effects on Akt signaling modulation in central nervous system of young and aged healthy rats

Abstract

Dehydroepiandrosterone (DHEA) is a steroid synthesized in adrenal cortex as well as in the nervous system. DHEA effects on central nervous system (CNS) have been associated with several brain functions such as marked neurotrophic and neuroprotective activity. DHEA plasma concentration decreases steadily with aging and studies have reported an inverse correlation between levels of DHEA and neurological diseases age-associated. Nonetheless, its mechanisms of action are not yet fully understood. Akt signaling pathway is one protein kinase which has been related to be DHEA modulated. The goal of this study was to investigate whether short-term (6 or 24 h) or chronic (5 weeks) DHEA treatment modulates Akt in CNS of adult (3 months) and aged (18 and 24 months) healthy rats. Hypothalamus and hippocampus homogenates were prepared to quantify total-Akt and phosphorylated Akt at Ser 473 (pAkt). The results here presented have shown that acute (50 mg/kg) and chronic (10 mg/kg) DHEA injections modulate total and pAkt levels. This effect was dose and time-dependent as well as age and tissue-dependent. In addition, the age variable also intervenes on total and pAkt levels expression independently of DHEA treatment.