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Published on: July 12, 2024
Microbial reconstitution reverses prenatal stress-induced cognitive impairment and synaptic deficits in rat offspring
Jie Chen1, Ru Zeng1, Huimin Chen2
1Department of Anatomy and Neurobiology, School of Basic Medical Sciences, Central South University, 172th Tongzipo Road, Changsha, Hunan, 410013, China.
Insights
Pregnancy stress alters gut bacteria, impairing offspring cognitive function. Restoring maternal gut microbiota with probiotics can reverse these negative effects, improving neural development.
Area of Science:
- Neuroscience
- Microbiology
- Developmental Biology
Background:
- Maternal stress during pregnancy is associated with neurodevelopmental disorders in offspring.
- The gut microbiome's role in mediating the effects of maternal stress on fetal brain development is not fully understood.
Purpose of the Study:
- To investigate the impact of gestational stress on maternal gut microbiota and its subsequent effects on offspring cognitive function.
- To identify the mechanisms by which gut dysbiosis influences fetal brain development and to explore potential therapeutic interventions.
Main Methods:
- Gestational stress was induced in pregnant rats.
- Fecal microbiota transplantation was performed from stressed to non-stressed pregnant rats.
- Levels of β-guanidinopropionic acid (BGP) were measured.
- Activation of AMPK and STAT3 signaling pathways in the fetal brain was assessed.
- Probiotic interventions were administered to stressed pregnant rats.
Main Results:
- Gestational stress induced gut microbial dysbiosis and cognitive impairment in offspring.
- Transplantation of cecal contents from stressed to normal pregnant rats reproduced cognitive deficits in offspring.
- Gut dysbiosis led to increased blood BGP levels, activating AMPK and STAT3 in the fetal brain.
- BGP supplementation mimicked stress-induced glial differentiation and impaired neural development.
- Probiotic treatment corrected cognitive impairment and synaptic deficits in offspring of stressed mothers.
Conclusions:
- Gestational stress-induced cognitive impairment in offspring is mediated by gut microbial dysbiosis.
- β-guanidinopropionic acid plays a key role in linking gut dysbiosis to fetal brain alterations.
- Microbial reconstitution through probiotics offers a promising therapeutic strategy to reverse the adverse effects of maternal stress on offspring neurodevelopment.
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.
