Complex and region-specific changes in astroglial markers in the aging brain.

Morphological aging of astrocytes was investigated in entorhinal cortex (EC), dentate gyrus (DG), and cornu ammonis 1 (CA1) regions of hippocampus of male SV129/C57BL6 mice of different age groups (3, 9, 18, and 24 months). Astroglial profiles were visualized by immunohistochemistry by using glial fibrillary acidic protein (GFAP), glutamine synthetase (GS), and s100β staining; these profiles were imaged using confocal or light microscopy for subsequent morphometric analysis. GFAP-positive profiles in the DG and the CA1 of the hippocampus showed progressive age-dependent hypertrophy, as indicated by an increase in surface, volume, and somata volume at 24 months of age compared with 3-month-old mice. In contrast with the hippocampal regions, aging induced a decrease in GFAP-positive astroglial profiles in the EC: the surface, volume, and cell body volume of astroglial cells at 24 months of age were decreased significantly compared with the 3-month group. The GS-positive astrocytes displayed smaller cellular surface areas at 24 months compared with 3-month-old animals in both areas of hippocampus, whereas GS-positive profiles remained unchanged in the EC of old mice. The morphometry of s100β-immunoreactive profiles revealed substantial increase in the EC, more moderate increase in the DG, and no changes in the CA1 area. Based on the morphological analysis of 3 astroglial markers, we conclude that astrocytes undergo a complex age-dependent remodeling in a brain region-specific manner.