Regional and laminar differences in antigen profiles and spatial distributions of astrocytes in the mouse hippocampus, with reference to aging

The heterogeneity of astrocytes is of growing interest, because this information is now considered to be crucial for understanding the diverse roles of astrocytes, for example, support and nutrition for neurons, and modulation of synaptic plasticity. In this study, we stereologically estimated the regional and laminar differences in antigen profiles and spatial distributions of astrocytes in the young adult (2-month-old) and middle-aged (10-month-old) mouse hippocampus. Here we used two established astrocyte markers, that is, glial fibrillary acidic protein (GFAP) and S100β, to identify the astrocyte population. In addition, we examined the patterns of expression of sex determining region Y-box 2 (Sox2) in the hippocampus. The majority of astrocytes expressed Sox2, and few regional and laminar differences were observed in the expression ratios of Sox2 in astrocytes. GFAP-negative astrocytes were specifically seen in the strata pyramidale and lucidum of the ventral CA3 region. S100β-negative astrocytes were mainly found in the hilus of the dorsal and ventral dentate gyrus. Antigen profiles of astrocytes defined by Sox2, GFAP, and S100β were rather constant until middle age. We then estimated the heterogeneity in spatial distributions of astrocytes. The numbers of astrocytes in the stratum lacunosum-moleculare of the dorsal part of Ammon's horn were significantly larger in the middle-aged mice than in young adult mice. On the contrary, the astrocyte numbers in the stratum oriens of Ammon's horn showed significant age-dependent decline. Despite such changes, the total number of astrocytes in the whole area of the hippocampus showed no differences between young adult and middle-aged mice. The present data may work as an essential anatomical reference to understand the heterogeneity of astrocytes in the hippocampus.