Brain region and cell specificity of B4GALT6 in mice with depressive-like behavior: A pilot study

doi:10.5498/wjp.v15.i10.109425

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World Journal of Psychiatry

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2220-3206

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

Basic Study

World J Psychiatry. Oct 19, 2025; 15(10): 109425
Published online Oct 19, 2025. doi: 10.5498/wjp.v15.i10.109425

Brain region and cell specificity of B4GALT6 in mice with depressive-like behavior: A pilot study

Shi-Na Zhang, Di Luan, Bo-Yang Sheng, Bing Xie, Le Xiao

Shi-Na Zhang, Bing Xie, Le Xiao, Department of Rehabilitation Medicine, The First Hospital of Changsha (The Affiliated Changsha Hospital of Xiangya School of Medicine, Central South University), Changsha 410005, Hunan Province, China

Di Luan, Department of Neurology, School of Medicine, Southeast University, Nanjing 210009, Jiangsu Province, China

Bo-Yang Sheng, School of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha 410208, Hunan Province, China

Co-corresponding authors: Le Xiao and Bing Xie.

Author contributions: Xiao L and Xie B contributed equally to this study as co-corresponding authors; Zhang SN and Xiao L were responsible for conceptualization, methodology, formal analysis, investigation, data curation, writing – original draft, writing - review & editing, supervision, and project administration; Luan D was responsible for conceptualization, methodology, formal analysis, investigation, data curation, writing – original draft, and writing - review & editing; Sheng BY was responsible for conceptualization, formal analysis, writing – original draft, and visualization; Xie B was responsible for conceptualization, formal analysis, writing – original draft, writing – review & editing supervision, and project administration.

Supported by Hunan Provincial Natural Science Foundation of China, No. 2025JJ80473 and No. 2025JJ80484; and the Institute of Hospital Management, National Health Commission of China, Major Project, No. SZ2024HL021.

Institutional animal care and use committee statement: This study was approved by the Experimental Animal Ethics Committee of Southeast University, with approval No. 20220104003.

Conflict-of-interest statement: The authors declare that there are no conflicts of interest.

ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.

Data sharing statement: The authors confirm that the data supporting the findings of this study are available within the article and its supplementary materials.

Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/

Corresponding author: Le Xiao, BS, Chief Physician, Department of Rehabilitation Medicine, The First Hospital of Changsha (The Affiliated Changsha Hospital of Xiangya School of Medicine, Central South University), No. 311 Yingpan Road, Kaifu District, Changsha 410005, Hunan Province, China. xlcssdyy@126.com

Received: May 12, 2025
Revised: June 27, 2025
Accepted: August 8, 2025
Published online: October 19, 2025
Processing time: 139 Days and 1.2 Hours

Abstract

BACKGROUND

Major depressive disorder (MDD) is a significant psychiatric condition that poses a serious threat to human life, primarily due to its association with suicidal behavior. The single nucleotide polymorphism rs372369000 is a risk locus for MDD and is located within the B4GALT6 gene. However, the biological and pathological implications of B4GALT6 in the brain concerning MDD remain unclear.

AIM

To reveal the biological and pathological significance of B4GALT6 in the brain and MDD.

METHODS

An inflammation-associated depression mouse model was developed by treating mice with lipopolysaccharides. B4GALT6-like immunoreactivity distribution and expression level was examined throughout the brain.

RESULTS

B4GALT6-like immunoreactivity increased in the hippocampus, PrL, and the visual cortex V1 region of MDD mice. This elevation varied across different brain subregions and cell types. Specifically, pathological alterations in B4GALT6-like immunoreactivity were observed in CA1 microglia, CA2 neurons, CA3 microglia and neurons, as well as V1 microglia and astrocytes. These changes correlated with the pathology of depression.

CONCLUSION

Although the neuropathological role of B4GALT6 in the brain remains to be fully characterized, B4GALT6 may be a potential therapeutic target for MDD.

Keywords: Major depressive disorder; rs372369000; B4GALT6; Potential therapeutic target; Gene expression

Core Tip: Major depressive disorder (MDD) poses a serious threat to human life. The single nucleotide polymorphism rs372369000 located within the B4GALT6 gene is a risk locus for MDD. However, the pathological mechanism of B4GALT6 in the brain in relation to MDD remains unclear. We developed an inflammation-associated depression model and examined B4GALT6-like immunoreactivity distribution and levels throughout the brain. The expression of B4GALT6-like immunoreactivity increased in the hippocampus, PrL, and the visual cortex V1 region of MDD mice. This elevation varied across different brain subregions and cell types. Taken together, our data suggest that B4GALT6 may be a potential therapeutic target for MDD.