BRAIN PLASTICITY IN AGING: EFFECT OF DIETARY RESTRICTION AND ANESTHESIA

The aim of this project is to examine the impact of (A) dietary restriction and (B) anesthesia on the mechanisms underlying plasticity-related processes in the aging brain. Dietary restriction (DR) is currently the only environmental intervention shown to attenuate age-related changes and promote late neuronal plasticity and neurogenesis. The effects of different types of DR on neural plasticity of the aging brain will be characterized through changes in cholesterol metabolism and neurotrophic signaling. The potential beneficial effects of DR will also be assessed in a pathological context, after cortical injury. We expect to elucidate the cellular and molecular mechanisms underlying the beneficial effects of reduced food intake on neural plasticity and point to the possible therapeutic application of DR in aging and post-injury recovery. Brain capacity for plastic changes will also be assessed in response to general anesthetics whose adverse toxic effects on the brain are well documented. We will examine the mechanisms of propofol-induced changes in developing and senescent brain in order to determine its effects on proapoptotic vs. prosurvival pathways. This will reveal the molecular and cellular mechanisms of propofol toxicity and/or plasticity in the young and elderly and will allow for an improved clinical application of anesthetics. On the whole, the results of this project should pave the way towards preservation and improvement of brain plasticity in aging.