2. Academic Validation
  3. Microbial reconstitution reverses prenatal stress-induced cognitive impairment and synaptic deficits in rat offspring

Microbial reconstitution reverses prenatal stress-induced cognitive impairment and synaptic deficits in rat offspring

  • Brain Behav Immun. 2024 Jun 6:120:231-247. doi: 10.1016/j.bbi.2024.06.005.
Jie Chen 1,  Ru Zeng 1,  Huimin Chen 2,  Mengya Cao 3,  Yihan Peng 1,  Jianbin Tong 4,  Jufang Huang 5
Affiliations

Affiliations

  • 1 Department of Anatomy and Neurobiology, School of Basic Medical Sciences, Central South University, 172th Tongzipo Road, Changsha, Hunan, 410013, China.
  • 2 Department of Anesthesiology, The First People's Hospital of Yunnan Province, No.127, Jinbi Road, Xishan District, Kunming, Yunnan, China.
  • 3 Department of Anesthesiology, Third Xiangya Hospital, Central South University, 138th Tongzipo Road, Changsha, Hunan, 410013, China.
  • 4 Department of Anesthesiology, Third Xiangya Hospital, Central South University, 138th Tongzipo Road, Changsha, Hunan, 410013, China; Hunan Province Key Laboratory of Brain Homeostasis, Third Xiangya Hospital, Central South University, 138th Tongzipo Road, Changsha, Hunan, 410013, China. Electronic address: jianbintong@csu.edu.cn.
  • 5 Department of Anatomy and Neurobiology, School of Basic Medical Sciences, Central South University, 172th Tongzipo Road, Changsha, Hunan, 410013, China. Electronic address: huangjufang@csu.edu.cn.
PMID: 38851306 DOI: 10.1016/j.bbi.2024.06.005
Abstract

Stress during pregnancy is often linked with increased incidents of neurodevelopmental disorders, including cognitive impairment. Here, we report that stress during pregnancy leads to alterations in the intestinal flora, which negatively affects the cognitive function of offspring. Cognitive impairment in stressed offspring can be reproduced by transplantation of cecal contents of stressed pregnant rats (ST) to normal pregnant rats. In addition, gut microbial dysbiosis results in an increase of β-guanidinopropionic acid in the blood, which leads to an activation of the adenosine monophosphate-activated protein kinase (AMPK) and signal transducer and activator of transcription 3 (STAT3) in the fetal brain. Moreover, β-guanidinopropionic acid supplementation in pregnant rats can reproduce pregnancy stress-induced enhanced glial differentiation of the fetal brain, resulting in impaired neural development. Using probiotics to reconstruct maternal microbiota can correct the cognitive impairment in the offspring of pregnant stressed rats. These findings suggest that microbial reconstitution reverses gestational stress-induced cognitive impairment and synaptic deficits in male rat offspring.

Keywords

AMPK; Cognitive impairment; GPA; Microbiota; Prenatal stress.

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