Contribution of hippocampal BDNF/CREB signaling pathway and gut microbiota to emotional behavior impairment induced by chronic unpredictable mild stress during pregnancy in rats offspring

Author:

Zhao Feng1234,Wang Kai23,Wen Yujun1,Chen Xiaohui23,Liu Hongya23,Qi Faqiu23,Fu Youjuan23,Zhu Jiashu23,Guan Suzhen123,Liu Zhihong23

Affiliation:

1. Ningxia Key Laboratory of Cerebrocranial Disease, Ningxia Medical University, Yinchuan, Ningxia, China

2. Key Laboratory of Environmental Factors and Chronic Disease Control, Ningxia Medical University, Yinchuan, Ningxia, China

3. School of Public Health and Management, Ningxia Medical University, Yinchuan, Ningxia, China

4. School of Public Health, Chongqing Medical University, Chongqing, China, Chongqing Medical University, Chongqing, China

Abstract

Background Numerous studies have shown that exposure to prenatal maternal stress (PMS) is associated with various psychopathological outcomes of offspring. The accumulating evidence linking bacteria in the gut and neurons in the brain (the microbiota-gut-brain axis) has been aconsensus; however, there is a lack of research on the involvement mechanism of gut microbiota in the regulation of the BDNF/CREB signaling pathway in the hippocampus of prenatally stressed offspring. Methods Pregnant rats were subjected to chronic unpredictable mild stress (CUMS) to establish the prenatal maternal stress model. The body weight was measured and the behavioral changes were recorded. Offspring were tested to determine emotional state using sucrose preference test (SPT), open-field test (OFT) and suspended tail test (STT). Gut microbiota was evaluated by sequencing the microbial 16S rRNA V3–V4 region, and the interactive analysis of bacterial community structure and diversity was carried out. The expression of hippocampal BDNF, TrkB and CREB mRNA and proteins were respectively measured using RT-PCR and Western blotting. Results Prenatal maternal stress increased maternal plasma corticosterone levels, slowed maternal weight gain and caused depression-like behaviors (all P < 0.05). In offspring, prenatal maternal stress increased plasma corticosterone levels (P < 0.05) and emotional behavior changes (depression-like state) were observed (P < 0.05). The species abundance, diversity and composition of the offspring’s gut microbiota changed after the maternal stress during pregnancy (P < 0.05). Compared with the control group’s offspring, the species abundance of Lactobacillaceae was dropped, while the abundance of the Muribaculaceae species abundance was risen. Concurrent, changes in the hippocampal structure of the offspring and decreases in expression of BDNF/CREB signaling were noted (P < 0.05). Conclusions Prenatal maternal stress leads to high corticosterone status and abnormal emotion behavior of offspring, which may be associated with the abnormal BDNF/CREB signaling in hippocampus of offspring caused by the change of gut microbiota composition.

Funder

National Natural Science Foundation of China No

Key Project of Ningxia Natural Science Foundation No

Key scientific research projects of natural science of Ningxia Medical University in 2020 No

Publisher

PeerJ

Subject

General Agricultural and Biological Sciences,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

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