Grant: Operating Grant

This research focuses on the metabolic mechanisms underlying trophic support for the maintenance of neuronal characteristics and function during the aging process. It will investigate the reasons for the known age-dependant vulnerability of a set of neurons of the central nervous system (CNS) supplying synaptic terminations to the cerebral cortex and playing an important role in higher CNS functions such as attention, learning and memory. There is not as yet an explanation for this marked vulnerability of these neurons to the aging process. Our laboratory has found a metabolic pathway responsible for the release, maturation and degradation of the trophic factor responsible for the maintenance of this set of CNS neurons. As a result, the investigations proposed consist of an array of multi-disciplinary studies including pharmacological, morphological, neurochemical and behavioral investigations to test the central hypothesis that a dysregulation of this metabolic pathway is responsible for the pronounced vulnerability to the brain aging process of this important set of CNS neurons. The investigations will serve as a model for other CNS systems, usually affected at later stages, and should shed some light on possible future therapeutic pharmacological manipulations to correct age-related neuronal deficits.