Abstract
SummaryWith age, neural stem cell (NSC) function in the adult ventricular-subventricular zone (V-SVZ) declines, reducing memory and cognitive function in males; however, the impact on females is not well understood. To obtain a global view of how age and sex impact the mouse V-SVZ, we constructed 3D montages after multiplex immunostaining, and used computer-based 3D image analysis to quantify data across the entire niche at 2, 18, and 22 months. We discovered dramatic sex differences in the aging of the V-SVZ niche vasculature, which regulates NSC activity: females showed increased diameter but decreased vessel density with age, while males showed decreased diameter and increased tortuosity and vessel density. Accompanying these vascular changes, males showed significant decline in NSC numbers, progenitor cell proliferation, and more disorganized migrating neuroblast chains with age; however, females did not. By examining the entire 3D niche, we found significant sex differences, with females being relatively spared through very old age.
Highlights
The ventricular-subventricular zone (V-SVZ) harbors neural stem cells (NSCs) that replenish neurons throughout life in the olfactory bulb in the adult mouse brain
Blood vessels within the V-SVZ are directly contacted by cells in the stem cell lineage, collectively called neural progenitor cells (NPCs)
Whole-mounts were stained with anti-laminin to label the basement membrane at the surface of the V-SVZ blood vessels, glial fibrillary acidic protein (GFAP) for type B NSCs, doublecortin (DCX) for type A neuroblasts, Ki67 for proliferating cells, beta catenin for ependymal cells, and 40,6-diamidino-2-phenylindole (DAPI) for cell nuclei. z Stack images were acquired through the entire depth of the V-SVZ germinal zone
Summary
The ventricular-subventricular zone (V-SVZ) harbors neural stem cells (NSCs) that replenish neurons throughout life in the olfactory bulb in the adult mouse brain. Less well studied is the response of the specialized V-SVZ vasculature which, as in other stem cell niches, plays a vital role. These observations have been made in aging males, so response of the niche and NSC lineage to aging in females is not known. The type B NSCs are situated mostly at the ependymal surface and project a long process to contact the blood vessel surface within the V-SVZ vascular plexus (Mirzadeh et al, 2008). How blood vessel parameters, such as diameter and tortuosity, change with age have not been examined in the V-SVZ
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