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

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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 https://t.co/IBn1cDwtY3 @thePeerJ
Biochemistry, Biophysics and Molecular Biology

Main article text

 

Introduction

Materials and Methods

Materials

Experimental animals

Apparatus and reagents

Methods

Chronic unpredictable mild stress (CUMS)

Mating

The grouping and feeding environment of offspring rats

Confirmation of the CUMS model during pregnancy

Measurement of maternal plasma corticosterone level

Sucrose preference test (SPT)

Open-field test (OFT)

Determination of emotional behavior changes in offspring

SPT and OFT

Suspended tail test (STT)

Collection of hippocampal tissue from offspring

Hematoxylin-Eosin (HE) staining

Quantitative real-time RT-PCR

  • BDNF: forward, 5′-TGTGGTCAGTGGCTGGCTCTC-3′, reverse, 5′-ACAGGACGGAAACAGAACGAACAG-3′

  • TrkB: forward, 5′-GGTCTATGCCGTGGTGGTGATTG-3′, reverse,5′-ATGTCTCGCCAACTTGAGCAGAAG-3′

  • CREB: forward,5′-GGAGCAGACAACCAGCAGAGTG-3′, reverse, 5′-GGCATGGATACCTGGGCTAATGTG-3′;

  • β-Actin: forward,5′-TGTCACCAACTGGGACGATA-3′, reverse, 5′-GGGGTGTTGAAGGTCTCAAA-3′.

Western blotting

Extract the total protein of hippocampus tissue

Bicinchoninic acid (BCA) method to measure protein concentration

The specific steps of western blotting

16S rRNA gene sequencing

Statistical analysis

Results

CUMS increases maternal plasma corticosterone levels

CUMS slowed down maternal weight gain

CUMS decreased maternal liquid consumption

CUMS reduced maternal horizontal and vertical movements

Body weight and plasma corticosterone level of offspring changed after maternal stress during pregnancy

Fluid consumption of offspring reduced after maternal stress during pregnancy

Horizontal and vertical movement of offspring descended after maternal stress during pregnancy

The immobility time of offspring increases after maternal stress during pregnancy

CUMS changes the maternal gut microbiota

CUMS reduces the species abundance and diversity of maternal gut microbiota

CUMS changes the species composition of maternal gut microbiota

Changes in the offspring’s gut microbiota after maternal stress during pregnancy

The species abundance and diversity of the offspring’s gut microbiota decreased after the maternal stress during pregnancy

The species composition of the offspring’s gut microbiota changed at the family level after the maternal stress during pregnancy

Hippocampal structure of offspring damaged due to maternal stress during pregnancy

BDNF/CREB signaling pathway of hippocampus changed in offspring after maternal stress during pregnancy

Correlation analysis between the genus level of gut microbiota and environmental factors

Discussion

Prenatal maternal stress changed the species composition and diversity of maternal gut microbiota

Changes in the offspring’s gut microbiota after prenatal maternal stress

Changes in the BDNF/CREB signaling pathway in the hippocampus of offspring after prenatal maternal stress

BDNF/CREB signaling pathway in hippocampus of offspring caused by the change of gut microbiota composition after prenatal maternal stress

Conclusions

Supplemental Information

Raw data for hormone levels, body weight, behavioural assays, and protein expression (Figures 1, 2, and 6).

DOI: 10.7717/peerj.13605/supp-1

Uncropped Gels/Blots.

DOI: 10.7717/peerj.13605/supp-3

Author Checklist.

DOI: 10.7717/peerj.13605/supp-4

Additional Information and Declarations

Competing Interests

The authors declare that they have no competing interests.

Author Contributions

Feng Zhao conceived and designed the experiments, performed the experiments, analyzed the data, prepared figures and/or tables, and approved the final draft.

Kai Wang performed the experiments, prepared figures and/or tables, and approved the final draft.

Yujun Wen analyzed the data, authored or reviewed drafts of the article, and approved the final draft.

Xiaohui Chen analyzed the data, authored or reviewed drafts of the article, and approved the final draft.

Hongya Liu analyzed the data, prepared figures and/or tables, and approved the final draft.

Faqiu Qi analyzed the data, authored or reviewed drafts of the article, and approved the final draft.

Youjuan Fu performed the experiments, prepared figures and/or tables, and approved the final draft.

Jiashu Zhu analyzed the data, prepared figures and/or tables, authored or reviewed drafts of the article, and approved the final draft.

Suzhen Guan conceived and designed the experiments, prepared figures and/or tables, and approved the final draft.

Zhihong Liu conceived and designed the experiments, analyzed the data, prepared figures and/or tables, and approved the final draft.

Animal Ethics

The following information was supplied relating to ethical approvals (i.e., approving body and any reference numbers):

Experimental operation complies with the relevant regulations of the ethics committee of the Animal Experimental Center of Ningxia Medical University (Number:IACUC-NYLAC-2019-089).

DNA Deposition

The following information was supplied regarding the deposition of DNA sequences:

The sequences are available at GenBank: PRJNA721070.

Data Availability

The following information was supplied regarding data availability:

The raw data is available in the Supplemental Files.

Funding

This study was supported by National Natural Science Foundation of China (No: 81960591), the Key Project of Ningxia Natural Science Foundation (No: 2022AAC02030), and the key scientific research projects of natural science of Ningxia Medical University in 2020 (No: XZ2020002). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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