Astrocyte diversity and aging in the mouse lemur primate brain

Abstract

Astrocytes play key roles in maintaining brain homeostasis, metabolism, and neurovascular integrity, yet their diversity and age-related modulation remain insufficiently understood, particularly across primate lineages. While rodent studies have generated extensive knowledge, notable species differences highlight the need for comparative analyses in non-human primates. The gray mouse lemur (Microcebus murinus), a small primate widely used in aging research, offers a valuable but underexplored model for studying astroglial aging. In this study, we characterized astrocyte distribution, morphology, and reactivity in 17 mouse lemurs aged 1.0-11.5 years using GFAP and vimentin immunohistochemistry. We identified marked regional and morphological heterogeneity, with dense astrocytic labeling in white matter, hippocampus, and sparse but diverse cortical populations. Distinct astrocyte subtypes--including fibrous, protoplasmic, projection, pial and subpial interlaminar, radial glia-like cells, tanycytes--were documented. Varicosity-bearing processes were common across multiple astroglial subtypes and may indicate altered physiological states. Quantitative analyses revealed pronounced age-related increases in astrocytic reactivity, particularly in white matter and interlaminar astrocytes. Cortical and hippocampal changes were comparatively modest. These findings indicate region-specific astrocytic vulnerability during aging and support the translational value of the mouse lemur for investigating glial aging in primates. Main PointsO_LIThe mouse lemur is the smallest primate on earth with a key role to understand primate brain characteristics. C_LIO_LIWe characterized seven different astrocyte subtypes: from fibrous to primate-specific astrocyte as interlaminar astrocytes in different brain regions of this primate. C_LIO_LIVaricosities were reported in different astrocyte subtypes found close to brain borders. C_LIO_LIMain age-related changes concerned fibrous astrocytes in the white matter and interlaminar astrocytes at the cortical border. C_LI