Both decreased Akt expression and mTOR phosphorylation are related to decreased neuronal differentiation in the hippocampal alveus of aged mice.

Abstract

Aging is an inevitable process which results in many changes. These changes are closely related to the hippocampus which is in charge of long-term learning and episodic memory. This study was to investigate age-related changes of the cell proliferation, neuroblast differentiation and Akt/mTOR signaling in the hippocampal alveus of aged mice. In the present study, we compared the differences of neurogenesis in the hippocampal alveus between adult (postnatal month 6) and aged (postnatal month 24) mice using immunohistochemistry and western blot analysis. The cell proliferation, neuroblast differentiation, and the increased astrocyte activation in the hippocampal alveus of mice were decreased in an age-dependent manner. In addition, during normal aging, the protein level of AKT, mTOR and the phosphorylation of mTOR were all decreased. However, the protein level of AKT was increased. These results indicate the neurogenesis in the immature neurons in the hippocampal alveus of aged mice was closely related to the normal aging process. In addition, during normal aging, the increased AKT phosphorylation and decreased mTOR phosphorylation in the hippocampus may play a role in aging development. The result indicates that increased activation of astrocyte, increased phosphorylation of AKT and decreased phosphorylation of mTOR may be involved in the decreased cell proliferation and neuroblast differentiation in the alveus of hippocampus of aged mice.