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Mol Psychiatry. 2014 Dec;19(12):1275-1283. doi: 10.1038/mp.2013.190. Epub 2014 Feb 11.

Stress and glucocorticoids promote oligodendrogenesis in the adult hippocampus.

Author information

1
Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, CA.
2
Department of Integrative Biology, University of California, Berkeley, Berkeley, CA.
3
Institute for Pediatric Regenerative Medicine, University of California, Davis, School of Medicine and Shriners Hospital, Sacramento, CA.
4
School of Public Health, University of California, Berkeley, Berkeley, CA.
5
Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA.
6
Department of Biological Sciences, Stanford University, Stanford, CA.
7
Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA.
8
Department of Neurosurgery, Stanford University, Stanford, CA.
#
Contributed equally

Abstract

Stress can exert long-lasting changes on the brain that contribute to vulnerability to mental illness, yet mechanisms underlying this long-term vulnerability are not well understood. We hypothesized that stress may alter the production of oligodendrocytes in the adult brain, providing a cellular and structural basis for stress-related disorders. We found that immobilization stress decreased neurogenesis and increased oligodendrogenesis in the dentate gyrus (DG) of the adult rat hippocampus and that injections of the rat glucocorticoid stress hormone corticosterone (cort) were sufficient to replicate this effect. The DG contains a unique population of multipotent neural stem cells (NSCs) that give rise to adult newborn neurons, but oligodendrogenic potential has not been demonstrated in vivo. We used a nestin-CreER/YFP transgenic mouse line for lineage tracing and found that cort induces oligodendrogenesis from nestin-expressing NSCs in vivo. Using hippocampal NSCs cultured in vitro, we further showed that exposure to cort induced a pro-oligodendrogenic transcriptional program and resulted in an increase in oligodendrogenesis and decrease in neurogenesis, which was prevented by genetic blockade of glucocorticoid receptor (GR). Together, these results suggest a novel model in which stress may alter hippocampal function by promoting oligodendrogenesis, thereby altering the cellular composition and white matter structure.

PMID:
24514565
PMCID:
PMC4128957
DOI:
10.1038/mp.2013.190
[Indexed for MEDLINE]
Free PMC Article

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