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 24h) 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 (50mg/kg) and chronic (10mg/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.

Attenuation of age-related changes in FOXO3a activity and the PI3K/Akt pathway by short-term feeding of ferulate

“…Another reported that phosphorylation of Akt at Ser 473 and Thr 308 was higher in the soleus muscles of very old rats (33 months) compared with 6-and 27-month-old rats (Wu et al 2009). In the hippocampus, the total Akt level increased and phosphorylated Akt expression was unaltered in 24-month-old rats compared to 3-month-old rats (Janner et al 2010). Unlike the hippocampus, the hypothalamus of 24-month-old rats showed an enhanced total Akt level after increased phosphorylation, while no significant alterations in total and phosphorylated Akt were found in 18-month-old animals (Janner et al 2010).…”

4-hydroxynonenal-mediated signaling and aging

“…Accumulating evidence suggests that AKT signaling changes with aging and the variation seems tissue dependent [72]. For example, AKT phosphorylation (at Ser473) and activity were significantly declined in the elderly in mice hippocampus (6 months vs 20 months) [73], skeletal muscle of human [74], but increased the old in rat soleus muscles (6 months vs 33 months) [75] and hypothalamus (6 months vs 24 months) [76]. …”

Human tissue kallikrein 1 ameliorates erectile function via modulation of macroautophagy in aged transgenic rats

“…Activation of the PI3K/AKT signaling pathway inhibits the action of tuberous sclerosis complex (TSC) by phosphorylating TSC2, which activates mTOR (Inoki et al, 2002). Many studies have reported that Akt levels are upregulated in the tissues of aged animals, such as rat kidneys (Kim et al, 2008), hypothalamus (Janner et al, 2010), and soleus muscles (Wu et al, 2009). Miyauchi et al (2004) have demonstrated that the activity of Akt increases along with the aging process of cells, and that Akt inhibition extends the longevity of primary endothelial cells (Miyauchi et al, 2004).…”

“…(D) The expression levels of PI3K, AKT, mTOR, p-PI3K, p-AKT, p-mTOR, with b-actin as the loading control, in the corpus cavernosum of the three groups are presented as bar graphs. Many studies have reported that Akt levels are upregulated in the tissues of aged animals, such as rat kidneys (Kim et al, 2008), hypothalamus (Janner et al, 2010), and soleus muscles (Wu et al, 2009). *, # p < 0.05 when comparing yWTR group.…”