Estrogen and serotonin enhance stress-induced visceral hypersensitivity in female rats by up-regulating brain-derived neurotrophic factor in spinal cord.

Autor: Chen J; Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Psychotic Disorders, Shanghai, China., Li Q; Division of Gastroenterology and Hepatology, Internal Medicine, University of Texas Medical Branch, Galveston, TX, USA., Saliuk G; Division of Gastroenterology and Hepatology, Internal Medicine, University of Texas Medical Branch, Galveston, TX, USA., Bazhanov S; Division of Gastroenterology and Hepatology, Internal Medicine, University of Texas Medical Branch, Galveston, TX, USA., Winston JH; Division of Gastroenterology and Hepatology, Internal Medicine, University of Texas Medical Branch, Galveston, TX, USA.
Jazyk: angličtina
Zdroj: Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society [Neurogastroenterol Motil] 2021 Oct; Vol. 33 (10), pp. e14117. Date of Electronic Publication: 2021 Mar 11.
DOI: 10.1111/nmo.14117
Abstrakt: Background: We previously reported that female offspring of dams subjected to chronic prenatal stress (CPS) develop enhanced visceral hypersensitivity (VHS) following exposure to chronic stress in adult life that is mediated by up-regulation of spinal cord BDNF. The aims of this study were to examine the roles of estrogen receptor alpha (ERα) and an increase in spinal serotonin signaling in promoting this enhanced VHS in female rats and up-regulation of spinal cord BDNF transcription.
Methods: Pregnant dams were exposed to chronic stress from E11 until delivery. At 8 weeks, a chronic adult stress (CAS) protocol was applied for nine days.
Key Results: Ovariectomy before CAS or treatment with letrozole before and during CAS significantly prevented the development of enhanced VHS in female CPS+CAS rats. Intrathecal application of ERα siRNA significantly reduced VHS, decreased lumbar-sacral spinal cord expression of both ERα and BDNF, and reversed pro-transcriptional epigenetic modifications at BDNF promoter lX. Cerebrospinal fluid serotonin levels and 5HT3A receptor expression in the LS spinal cord were both significantly increased in female CPS+CAS rats. During CAS, intrathecal infusion of alosetron significantly decreased VHS, reduced BDNF and ERα expression in the LS spinal cord, and attenuated RNA pol II and ERα binding to the BNDF core promoter IX.
Conclusions & Inferences: Serotonin-mediated activation of 5HT3A receptors in the spinal cord drives the development of enhanced female-specific VHS in our two hit CPS+CAS through up-regulation of spinal cord ERα.
(© 2021 John Wiley & Sons Ltd.)
Databáze: MEDLINE
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