Koutmani Y, Gampierakis IA, Polissidis A, Ximerakis M, Koutsoudaki PN, Polyzos A, Agrogiannis G, Karaliota S, Thomaidou D, Rubin LL, Politis PK, Karalis KP. 2019. CRH Promotes the Neurogenic Activity of Neural Stem Cells in the Adult Hippocampus. Cell reports. 29(4):932-945.e7. Pubmed: 31644914 DOI:S2211-1247(19)31225-2


Local cues in the adult neurogenic niches dynamically regulate homeostasis in neural stem cells, whereas their identity and associated molecular mechanisms remain poorly understood. Here, we show that corticotropin-releasing hormone (CRH), the major mediator of mammalian stress response and a key neuromodulator in the adult brain, is necessary for hippocampal neural stem cell (hiNSC) activity under physiological conditions. In particular, we demonstrate functionality of the CRH/CRH receptor (CRHR) system in mouse hiNSCs and conserved expression in humans. Most important, we show that genetic deficiency of CRH impairs hippocampal neurogenesis, affects spatial memory, and compromises hiNSCs' responsiveness to environmental stimuli. These deficits have been partially restored by virus-mediated CRH expression. Additionally, we provide evidence that local disruption of the CRH/CRHR system reduces neurogenesis, while exposure of adult hiNSCs to CRH promotes neurogenic activity via BMP4 suppression. Our findings suggest a critical role of CRH in adult neurogenesis, independently of its stress-related systemic function.
Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.

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Lee Rubin investigates the key molecular mediators of a variety of neurodegenerative diseases, with the ultimate goal of finding effective preclinical therapeutic candidates.

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