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Hippocampal Crhr1 conditional gene knockout ameliorated the depression-like behavior and pathological damage in male offspring mice caused by chronic stress during pregnancy.
- Source :
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Behavioural brain research [Behav Brain Res] 2024 Aug 24; Vol. 472, pp. 115139. Date of Electronic Publication: 2024 Jul 03. - Publication Year :
- 2024
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Abstract
- Numerous studies have demonstrated that chronic stress during pregnancy (CSDP) can induce depression and hippocampal damage in offspring. It has also been observed that high levels of corticotropin-releasing hormone (CRH) can damage hippocampal neurons, and intraperitoneal injection of a corticotropin releasing hormone receptor 1 (CRHR1) antagonist decreases depression-like behavior and hippocampal neuronal damage in a mouse depression model. However, whether CSDP causes hippocampal damage and depression in offspring through the interaction of CRH and hippocampal CRHR1 remains unknown and warrants further investigation. Therefore, hippocampal Crhr1 conditional gene knockout mice and C57/BL6J mice were used to study these questions. Depression-related indexs in male offspring mice were examined using the forced swim test (FST), sucrose preference test (SPT), tail suspension test (TST) and open field test (OFT). Serum CRH levels were measured by enzyme-linked immunosorbent assay (ELISA). Golgi-Cox staining was used to examine the morphological changes of hippocampal neuronal dendrites. Neuronal apoptosis in the hippocampal CA3 regions was detected by terminal deoxynucleotidy transferase dUTP nick end labeling (TUNEL) staining. The levels of mammalian target of rapamycin (mTOR), phosphorylated mTOR (p-mTOR) and protein kinase B (AKT) proteins were measured by Western blot analysis. This study showed that CSDP induces depression-like behavior, hippocampal neuronal dendrite damage and apoptosis in male offspring mice. Conditional gene knockout of hippocampal Crhr1 in mice reduced CSDP-induced depression-like behavior, hippocampal neuronal dendrite damage and apoptosis in male offspring, and counteracted the CSDP-induced decreased expression of p-Akt and mTOR activity in male offspring hippocampus. These findings demonstrated that CSDP might inhibit the Akt/mTOR pathway by increasing the levels of CRH, leading to increased CRH-mediated activation of hippocampal CRHR1, thereby inducing synaptic impairment and apoptosis in hippocampal neurons, which in turn leads to depression-like behavior in offspring.<br />Competing Interests: Declaration of Competing Interest All authors declare they have no conflicts of interest.<br /> (Copyright © 2024 Elsevier B.V. All rights reserved.)
- Subjects :
- Animals
Female
Male
Pregnancy
Mice
Neurons metabolism
Neurons pathology
Apoptosis physiology
Disease Models, Animal
Behavior, Animal physiology
TOR Serine-Threonine Kinases metabolism
Receptors, Corticotropin-Releasing Hormone metabolism
Hippocampus metabolism
Hippocampus pathology
Stress, Psychological metabolism
Depression metabolism
Mice, Knockout
Mice, Inbred C57BL
Prenatal Exposure Delayed Effects
Corticotropin-Releasing Hormone metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1872-7549
- Volume :
- 472
- Database :
- MEDLINE
- Journal :
- Behavioural brain research
- Publication Type :
- Academic Journal
- Accession number :
- 38969017
- Full Text :
- https://doi.org/10.1016/j.bbr.2024.115139