Age-dependent effects of resveratrol in hypothalamic astrocyte cultures.

Abstract

The hypothalamus plays critical roles in maintaining brain homeostasis and increasing evidence has highlighted astrocytes orchestrating several of hypothalamic functions. However, it remains unclear how hypothalamic astrocytes participate in neurochemical mechanisms associated with aging process, as well as whether these cells can be a target for antiaging strategies. In this sense, the aim of this study is to evaluate the age-dependent effects of resveratrol, a well-characterized neuroprotective compound, in primary astrocyte cultures derived from the hypothalamus of newborn, adult, and aged rats. Male Wistar rats (2, 90, 180, and 365 days old) were used in this study. Cultured astrocytes from different ages were treated with 10 and 100 μM resveratrol and cellular viability, metabolic activity, astrocyte morphology, release of glial cell line-derived neurotrophic factor (GDNF), transforming growth factor β (TGF-β), tumor necrosis factor α (TNF-α), interleukins (IL-1β, IL-6, and IL-10), as well as the protein levels of Nrf2 and HO-1 were evaluated. In vitro astrocytes derived from neonatal, adults, and aged animals changed metabolic activity and the release of trophic factors (GDNF and TGF-β), as well as the inflammatory mediators (TNF-α, IL-1β, IL-6, and IL-10). Resveratrol prevented these alterations. In addition, resveratrol changed the immunocontent of Nrf2 and HO-1. The results indicated that the effects of resveratrol seem to have a dose- and age-associated glioprotective role. These findings demonstrate for the first time that resveratrol prevents the age-dependent underlying functional reprogramming of in vitro hypothalamic astrocytes, reinforcing its antiaging activity, and consequently, its glioprotective role.