دورية أكاديمية
Hippocampal Crhr1 conditional gene knockout ameliorated the depression-like behavior and pathological damage in male offspring mice caused by chronic stress during pregnancy.
| العنوان: | Hippocampal Crhr1 conditional gene knockout ameliorated the depression-like behavior and pathological damage in male offspring mice caused by chronic stress during pregnancy. |
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| المؤلفون: | Tao L; School of Public Health, Anhui Medical University, Hefei, Anhui 230032, China; Nanjing Jiangning District Center for Disease Control and Prevention, Nanjing 211100, China., Li XX; School of Public Health, Anhui Medical University, Hefei, Anhui 230032, China., Tu XR; School of Public Health, Anhui Medical University, Hefei, Anhui 230032, China., Liu R; School of Public Health, Anhui Medical University, Hefei, Anhui 230032, China., Xu JW; School of Public Health, Anhui Medical University, Hefei, Anhui 230032, China., Lv YL; Anhui Provincial Center for Disease Control and Prevention, Hefei, Anhui 230601, China., Yao YY; School of Public Health, Anhui Medical University, Hefei, Anhui 230032, China; Anhui Provincial Key Laboratory of Population Health & Aristogenics, Hefei, Anhui 230032, China. Electronic address: 1988500004@amhu.edu.cn. |
| المصدر: | Behavioural brain research [Behav Brain Res] 2024 Aug 24; Vol. 472, pp. 115139. Date of Electronic Publication: 2024 Jul 03. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier/North-Holland Biomedical Press Country of Publication: Netherlands NLM ID: 8004872 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1872-7549 (Electronic) Linking ISSN: 01664328 NLM ISO Abbreviation: Behav Brain Res Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Amsterdam, Elsevier/North-Holland Biomedical Press. |
| مواضيع طبية MeSH: | 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, Animals ; Female ; Male ; Pregnancy ; Mice ; Neurons/metabolism ; Neurons/pathology ; Apoptosis/physiology ; Disease Models, Animal ; Behavior, Animal/physiology ; TOR Serine-Threonine Kinases/metabolism |
| مستخلص: | 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. Competing Interests: Declaration of Competing Interest All authors declare they have no conflicts of interest. (Copyright © 2024 Elsevier B.V. All rights reserved.) |
| فهرسة مساهمة: | Keywords: CRH; CRHR1; Chronic stress during pregnancy; Depression; Hippocampus; mTOR |
| المشرفين على المادة: | 0 (Receptors, Corticotropin-Releasing Hormone) 5CLY6W2H1M (CRF receptor type 1) 9015-71-8 (Corticotropin-Releasing Hormone) EC 2.7.11.1 (TOR Serine-Threonine Kinases) |
| تواريخ الأحداث: | Date Created: 20240705 Date Completed: 20240812 Latest Revision: 20240812 |
| رمز التحديث: | 20240813 |
| DOI: | 10.1016/j.bbr.2024.115139 |
| PMID: | 38969017 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1872-7549 |
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| DOI: | 10.1016/j.bbr.2024.115139 |