title: Stress and glucocorticoids promote oligodendrogenesis in the adult hippocampus.
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.
authors: Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, CA.
authors: Sundari
authors: S
authors: Chetty
authors: Department of Integrative Biology, University of California, Berkeley, Berkeley, CA.
authors: Aaron R
authors: AR
authors: Friedman
authors: Department of Integrative Biology, University of California, Berkeley, Berkeley, CA.
authors: Kereshmeh
authors: K
authors: Taravosh-Lahn
authors: Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, CA.
authors: Elizabeth D
authors: ED
authors: Kirby
authors: Department of Integrative Biology, University of California, Berkeley, Berkeley, CA.
authors: Christian
authors: C
authors: Mirescu
authors: Institute for Pediatric Regenerative Medicine, University of California, Davis, School of Medicine and Shriners Hospital, Sacramento, CA.
authors: Fuzheng
authors: F
authors: Guo
authors: Department of Integrative Biology, University of California, Berkeley, Berkeley, CA.|School of Public Health, University of California, Berkeley, Berkeley, CA.
authors: Danna
authors: D
authors: Krupik
authors: Department of Integrative Biology, University of California, Berkeley, Berkeley, CA.
authors: Andrea
authors: A
authors: Nicholas
authors: Department of Integrative Biology, University of California, Berkeley, Berkeley, CA.
authors: Anna
authors: A
authors: Geraghty
authors: Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, CA.
authors: Amrita
authors: A
authors: Krishnamurthy
authors: Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, CA.
authors: Meng-Ko
authors: MK
authors: Tsai
authors: Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA.
authors: David
authors: D
authors: Covarrubias
authors: Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, CA.
authors: Alana
authors: A
authors: Wong
authors: Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, CA.|School of Public Health, University of California, Berkeley, Berkeley, CA.
authors: Darlene
authors: D
authors: Francis
authors: Department of Biological Sciences, Stanford University, Stanford, CA.|Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA.
authors: Robert M
authors: RM
authors: Sapolsky
authors: Department of Neurosurgery, Stanford University, Stanford, CA.
authors: Theo D
authors: TD
authors: Palmer
authors: Institute for Pediatric Regenerative Medicine, University of California, Davis, School of Medicine and Shriners Hospital, Sacramento, CA.
authors: David
authors: D
authors: Pleasure
authors: Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, CA.|Department of Integrative Biology, University of California, Berkeley, Berkeley, CA.
authors: Daniela
authors: D
authors: Kaufer
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D049109:Cell Proliferation / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D003345:Corticosterone / Q000008:administration & dosage / Q000378:metabolism*; D004195:Disease Models, Animal; D005938:Glucocorticoids / Q000008:administration & dosage / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008822:Mice, Transgenic; D064231:Nestin / Q000235:genetics / Q000378:metabolism; D058953:Neural Stem Cells / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D009836:Oligodendroglia / Q000187:drug effects / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors / Q000378:metabolism; D012149:Restraint, Physical; D013315:Stress, Psychological / Q000503:physiopathology*
chemical_list: D005938:Glucocorticoids; C577485:Nes protein, mouse; D064231:Nestin; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D003345:Corticosterone