title: Neurogenic Niche Microglia Undergo Positional Remodeling and Progressive Activation Contributing to Age-Associated Reductions in Neurogenesis.
abstract: Neural stem cells (NSCs) exist throughout life in the ventricular-subventricular zone (V-SVZ) of the mammalian forebrain. During aging NSC function is diminished through an unclear mechanism. In this study, we establish microglia, the immune cells of the brain, as integral niche cells within the V-SVZ that undergo age-associated repositioning in the V-SVZ. Microglia become activated early before NSC deficits during aging resulting in an antineurogenic microenvironment due to increased inflammatory cytokine secretion. These age-associated changes were not observed in non-neurogenic brain regions, suggesting V-SVZ microglia are specialized. Using a sustained inflammatory model in young adult mice, we induced microglia activation and inflammation that was accompanied by reduced NSC proliferation in the V-SVZ. Furthermore, in vitro studies revealed secreted factors from activated microglia reduced proliferation and neuron production compared to secreted factors from resting microglia. Our results suggest that age-associated chronic inflammation contributes to declines in NSC function within the aging neurogenic niche.
authors: 1 Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio , San Antonio, Texas.|2 Barshop Institute for Longevity and Aging Studies , San Antonio, Texas.
authors: Rene
authors: R
authors: Solano Fonseca
authors: 1 Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio , San Antonio, Texas.
authors: Swetha
authors: S
authors: Mahesula
authors: 1 Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio , San Antonio, Texas.|2 Barshop Institute for Longevity and Aging Studies , San Antonio, Texas.
authors: Deana M
authors: DM
authors: Apple
authors: 3 Molecular and Translational Medicine, Boston University , Boston, Massachusetts.
authors: Rekha
authors: R
authors: Raghunathan
authors: 4 Department of Pharmacology, University of Texas Health Science Center at San Antonio , San Antonio, Texas.
authors: Allison
authors: A
authors: Dugan
authors: 5 Department of Biology, University of Texas at San Antonio , San Antonio, Texas.
authors: Astrid
authors: A
authors: Cardona
authors: 4 Department of Pharmacology, University of Texas Health Science Center at San Antonio , San Antonio, Texas.
authors: Jason
authors: J
authors: O'Connor
authors: 1 Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio , San Antonio, Texas.|2 Barshop Institute for Longevity and Aging Studies , San Antonio, Texas.
authors: Erzsebet
authors: E
authors: Kokovay
mesh_terms: D000818:Animals; D001921:Brain / Q000166:cytology / Q000254:growth & development*; D002478:Cells, Cultured; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000166:cytology* / Q000378:metabolism; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism; D055495:Neurogenesis; D055153:Stem Cell Niche