Grant Description:
This project melds our findings that 1) aging in F344 male rats is accompanied by impairments on hippocampus-sensitive learning tasks but by maintenance or even enhancement on striatum-sensitive learning tasks, 2) astrocytic production of lactate is impaired in aged male rats in the hippocampus but maintained in the striatum, and 3) that glucose and lactate infusions directly into the hippocampus fully reverse the age-related impairments. The goal of this project is to determine the locus of the loss of lactate production, i.e. whether by decreased norepinephrine release or by decreased action on the beta2 adrenergic receptors found on astrocytes where they regulation glycogenolysis and lactate production. Additionally, we found that female rats have the opposite trajectory of cognitive changes, decreased striatal and maintained hippocampal functions. This project will apply the measurements and manipulations of astrocytes in female rats to determine whether the age-related trajectory of changes in lactate production in females is, like the behavioral results, opposite that of males.