Date of Award

5-1-2012

Degree Name

Master of Science

Department

Molecular Cellular and Systemic Physiology

First Advisor

Patrylo, Peter

Abstract

During aging, a decline in metabolism appears to be associated with altered hippocampal function. Thus, 1-13C-glucose and 2-13C-acetate were employed to assess neural metabolism in the dentate gyrus and CA1 of F344 rats with respect to aging and cognitive status. The results obtained when 1-13C-glucose was used as the metabolic substrate suggest that glucose metabolism may not be altered in neural tissue itself with respect to aging or a decline in hippocampal function. In contrast, the use of 2-13C-acetate, a substrate that is preferentially metabolized by astrocytes, revealed significantly increased astroglial metabolism associated with age and preserved hippocampal function. Specifically, greater 2-13C-acetate incorporation into glutamine and glutamate was observed in the dentate gyrus and CA1 of aged rats that performed similar to young rats in the Morris water maze task. Since glutamate is the primary excitatory neurotransmitter of the hippocampus and plays a central role in synaptic plasticity, the mechanism proposed to underlie learning and memory, these finding were taken to represent an adaptive metabolic response by astroglia in the aged hippocampus. Subsequently, astroglia metabolism could potentially be a future target of therapeutic strategies for age-related cognitive decline.

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