Complex and regional-specific changes in the morphological complexity of GFAP+ astrocytes in middle-aged mice.

During aging, alterations in astrocyte phenotype occur in areas associated with age-related cognitive decline, including hippocampus. Previous work also reported subregion-specific changes in surface, volume and soma size of hippocampal astrocytes during physiological aging. Herein we extensively analyzed, by morphometric analysis, fine morphological features of GFAP+ astrocytes in young (6-month-old) and middle-aged (14-month-old) male mice. We observed remarkable heterogeneity in the astrocytic response to aging in distinct subfields and along the dorso-ventral axis of the hippocampus and in the entorhinal cortex (EC). Specifically, in middle-aged mice dorsal granule cell and molecular layers, but not dorsal hilus, astrocytes underwent remarkable increase in their morphological complexity. These changes were absent in ventral Dentate Gyrus (vDG). In addition, in EC, the major input to dorsal DG (dDG), astrocytes underwent remarkable atrophic changes in middle-aged mice. Since dDG, and not vDG, is involved in cognitive functions, these findings appear worth of further evaluation. Our findings also suggest an additional level of complexity in the structural changes associated with brain aging.