Neural stem and progenitor cells support and protect adult hippocampal function via vascular endothelial growth factor secretion.

Autor: Miller LN; Department of Psychology, The Ohio State University, Columbus, OH, USA., Walters AE; Department of Psychology, The Ohio State University, Columbus, OH, USA., Denninger JK; Department of Psychology, The Ohio State University, Columbus, OH, USA., Hanson MA; Department of Neuroscience, The Ohio State University, Columbus, OH, USA., Marshall AH; Department of Neuroscience, The Ohio State University, Columbus, OH, USA., Johantges AC; Department of Neuroscience, The Ohio State University, Columbus, OH, USA., Hosawi M; Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA, USA., Sebring G; Department of Psychology, The Ohio State University, Columbus, OH, USA., Rieskamp JD; Department of Psychology, The Ohio State University, Columbus, OH, USA., Ding T; Department of Psychology, The Ohio State University, Columbus, OH, USA., Rindani R; Department of Psychology, The Ohio State University, Columbus, OH, USA.; UC Health, Cincinnati, OH, USA., Chen KS; Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA, USA., Goldberg ME; Department of Psychology, The Ohio State University, Columbus, OH, USA., Senthilvelan S; Department of Psychology, The Ohio State University, Columbus, OH, USA., Volk A; Department of Psychology, The Ohio State University, Columbus, OH, USA., Zhao F; Department of Neuroscience, The Ohio State University, Columbus, OH, USA., Askwith C; Department of Neuroscience, The Ohio State University, Columbus, OH, USA., Wester JC; Department of Neuroscience, The Ohio State University, Columbus, OH, USA., Kirby ED; Department of Psychology, The Ohio State University, Columbus, OH, USA. kirby.224@osu.edu.; Chronic Brain Injury Center, The Ohio State University, Columbus, OH, USA. kirby.224@osu.edu.
Jazyk: angličtina
Zdroj: Molecular psychiatry [Mol Psychiatry] 2024 Nov 11. Date of Electronic Publication: 2024 Nov 11.
DOI: 10.1038/s41380-024-02827-8
Abstrakt: Adult neural stem and progenitor cells (NSPCs) reside in the dentate gyrus (DG) of the hippocampus throughout the lifespan of most mammalian species. In addition to generating new neurons, NSPCs may alter their niche via secretion of growth factors and cytokines. We recently showed that adult DG NSPCs secrete vascular endothelial growth factor (VEGF), which is critical for maintaining adult neurogenesis. Here, we asked whether NSPC-derived VEGF alters hippocampal function independent of adult neurogenesis. We found that loss of NSPC-derived VEGF acutely impaired hippocampal memory, caused neuronal hyperexcitability and exacerbated excitotoxic injury. Conversely, we observed that overexpression of VEGF reduced microglial response to excitotoxic injury. We also found that NSPCs generate substantial proportions of total DG VEGF and VEGF disperses widely throughout the DG, both of which help explain how this anatomically-restricted cell population could modulate function broadly. These findings suggest that NSPCs actively support and protect DG function via secreted VEGF, thereby providing a non-neurogenic functional dimension to endogenous NSPCs.
Competing Interests: Competing interests The authors declare no competing interests.
(© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)
Databáze: MEDLINE
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