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Baicalin Ameliorates Corticosterone-Induced Depression by Promoting Neurodevelopment of Hippocampal via mTOR/GSK3β Pathway

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Abstract

Objective

To investigate the role of hippocampal neurodevelopment in the antidepressant effect of baicalin.

Methods

Forty male Institute of Cancer Research mice were divided into control, corticosterone (CORT, 40 mg/kg), CORT+baicalin-L (25 mg/kg), CORT+baicalin-H (50 mg/kg), and CORT+fluoxetine (10 mg/kg) groups according to a random number table. An animal model of depression was established by chronic CORT exposure. Behavioral tests were used to assess the reliability of depression model and the antidepressant effect of baicalin. In addition, Nissl staining and immunofluorescence were used to evaluate the effect of baicalin on hippocampal neurodevelopment in mice. The protein and mRNA expression levels of neurodevelopment-related factors were detected by Western blot analysis and real-time polymerase chain reaction, respectively.

Results

Baicalin significantly ameliorated the depressive-like behavior of mice resulting from CORT exposure and promoted the development of dentate gyrus in hippocampus, thereby reversing the depressive-like pathological changes in hippocampal neurons caused by CORT neurotoxicity. Moreover, baicalin significantly decreased the protein and mRNA expression levels of glycogen synthase kinase 3β (GSK3β), and upregulated the expression levels of cell cycle protein D1, p-mammalian target of rapamycin (mTOR), doublecortin, and brain-derived neurotrophic factor (all P<0.01). There were no significant differences between baicalin and fluoxetine groups (P>0.05).

Conclusion

Baicalin can promote the development of hippocampal neurons via mTOR/GSK3β signaling pathway, thus protect mice against CORT-induced neurotoxicity and play an antidepressant role.

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Authors and Affiliations

Authors

Contributions

Wang Z and Cheng YT performed the experiments and wrote the manuscript. Lu Y and Sun GQ analyzed the data. Pei L designed the study and amended the paper.

Corresponding author

Correspondence to Lin Pei.

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The authors declare no competing interests.

Additional information

Supported by the National Key Research and Development Program (No. 2017YFC1701701) and the Postgraduate Innovation Funding Project of Hebei University of Chinese Medicine (No. XCXZZBS2020005)

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Wang, Z., Cheng, Yt., Lu, Y. et al. Baicalin Ameliorates Corticosterone-Induced Depression by Promoting Neurodevelopment of Hippocampal via mTOR/GSK3β Pathway. Chin. J. Integr. Med. 29, 405–412 (2023). https://doi.org/10.1007/s11655-022-3590-z

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