title: Corticotropin-releasing hormone exerts direct effects on neuronal progenitor cells: implications for neuroprotection.
abstract: Neurogenesis during embryonic and adult life is tightly regulated by a network of transcriptional, growth and hormonal factors. Emerging evidence indicates that activation of the stress response, via the associated glucocorticoid increase, reduces neurogenesis and contributes to the development of adult diseases.As corticotrophin-releasing hormone (CRH) or factor is the major mediator of adaptive response to stressors, we sought to investigate its involvement in this process. Accordingly, we found that CRH could reverse the damaging effects of glucocorticoid on neural stem/progenitor cells (NS/PCs), while its genetic deficiency results in compromised proliferation and enhanced apoptosis during neurogenesis. Analyses in fetal and adult mouse brain revealed significant expression of CRH receptors in proliferating neuronal progenitors. Furthermore, by using primary cultures of NS/PCs, we characterized the molecular mechanisms and identified CRH receptor-1 as the receptor mediating the neuroprotective effects of CRH. Finally, we demonstrate the expression of CRH receptors in human fetal brain from early gestational age, in areas of active neuronal proliferation. These observations raise the intriguing possibility for CRH-mediated pharmacological applications in diseases characterized by altered neuronal homeostasis, including depression, dementia, neurodegenerative diseases, brain traumas and obesity.
authors: Department of Developmental Biology, Center for Basic Research, Biomedical Research Foundation of the Academy of Athens, Athens, Greece.
authors: Y
authors: Y
authors: Koutmani
authors: P K
authors: PK
authors: Politis
authors: M
authors: M
authors: Elkouris
authors: G
authors: G
authors: Agrogiannis
authors: M
authors: M
authors: Kemerli
authors: E
authors: E
authors: Patsouris
authors: E
authors: E
authors: Remboutsika
authors: K P
authors: KP
authors: Karalis
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D003346:Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D003907:Dexamethasone / Q000037:antagonists & inhibitors / Q000633:toxicity; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D055495:Neurogenesis / Q000187:drug effects / Q000502:physiology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D018019:Receptors, Corticotropin-Releasing Hormone / Q000819:agonists / Q000378:metabolism / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013234:Stem Cells / Q000187:drug effects / Q000502:physiology*; D000099052:CRF Receptor, Type 1
chemical_list: D018696:Neuroprotective Agents; D011743:Pyrimidines; D011758:Pyrroles; D018019:Receptors, Corticotropin-Releasing Hormone; C103016:antalarmin; D000099052:CRF Receptor, Type 1; D003907:Dexamethasone; D003346:Corticotropin-Releasing Hormone
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