Astroglial atrophy associates with loss of nuclear S100A10 in the hippocampus of aged male tree shrews

Abstract Astrocytes are glial cells that participate in multiple physiological functions, such as protecting neurons against all types of damage. However, astrocytes develop morphological alterations during aging, such as decreased length, volume, and branch points of their processes, also known as astrocytic atrophy. Until now, the exact mechanism associated with the onset of atrophy is unknown. Tree shrew ( Tupaia belangeri ) is a long-lived animal from the Scadentia order that develops several age-dependent brain alterations. In this study, we analyzed the morphology of GFAP+ astrocytes in the hippocampal region of adult, old, and aged male tree shrews. Aged animals presented more GFAP+ astrocytes in the proximal subiculum, CA3, and CA2-CA1 subregions than younger animals, being significantly higher only in CA3. However, in aged subjects, the number of atrophic astrocytes was significantly higher in the dentate gyrus and CA2 subregion compared to old animals. Interestingly, in the proximal subiculum, astrocytes had a reduced arborization at all ages evaluated. S100A10, a protein overexpressed by neuroprotective-type astrocytes, was mainly found in the nucleus of astrocytes of adult and old subjects. However, in old and aged animals, S100A10 was located in the cytoplasmic compartment of atrophic astrocytes. Furthermore, in astrocytes of aged tree shrews, cytoplasmic inclusions of S100A10 colocalized with the nuclear export protein, Crm-1. These results suggest that the transport of S100A10 from the nucleus to the cytoplasmic compartment of astrocytes could be a process related to astroglial atrophy during the aging process in the hippocampus of three shrews.