Neurogenic niche microglia undergo positional remodeling and progressive activation contributing to age-associated reductions in neurogenesis

Rene Solano Fonseca, Swetha Mahesula, Deana M. Apple, Rekha Raghunathan, Allison Dugan, Astrid Cardona, Jason O'Connor, Erzsebet Kokovay

Research output: Contribution to journalArticlepeer-review

41 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)542-555
Number of pages14
JournalStem Cells and Development
Volume25
Issue number7
DOIs
StatePublished - Apr 1 2016

ASJC Scopus subject areas

  • Hematology
  • Developmental Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Neurogenic niche microglia undergo positional remodeling and progressive activation contributing to age-associated reductions in neurogenesis'. Together they form a unique fingerprint.

Cite this