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  2. γ-Aminobutyric acid promotes the inhibition of hair growth induced by chronic restraint stress

γ-Aminobutyric acid promotes the inhibition of hair growth induced by chronic restraint stress

  • Life Sci. 2023 Jan 31;317:121439. doi: 10.1016/j.lfs.2023.121439.
Xuewen Wang 1 Yixin Su 2 Zhenying Cai 1 Yaohan Xu 1 Xia Wu 1 Mus'ab Al Rudaisat 1 Chunting Hua 1 Siji Chen 1 Lihua Lai 2 Hao Cheng 3 Yinjing Song 4 Qiang Zhou 5
Affiliations

Affiliations

  • 1 Department of Dermatology and Venereology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China; Hair Research Center, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.
  • 2 Institute of Immunology, Zhejiang University School of Medicine, Hangzhou 310058, China; Liangzhu Laboratory, Zhejiang University Medical Center, China.
  • 3 Department of Dermatology and Venereology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China; Hair Research Center, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China. Electronic address: chenghao1@zju.edu.cn.
  • 4 Department of Dermatology and Venereology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China; Hair Research Center, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China. Electronic address: 3315023@zju.edu.cn.
  • 5 Department of Dermatology and Venereology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China; Hair Research Center, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China. Electronic address: 3197035@zju.edu.cn.
Abstract

Stress plays a critical role in hair loss, although the underlying mechanisms are largely unknown. γ-aminobutyric acid (GABA) has been reported to be associated with stress; however, whether it affects stress-induced hair growth inhibition is unclear. This study aimed to investigate the potential roles and mechanisms of action of GABA in chronic restraint stress (CRS)-induced hair growth inhibition. We performed RNA-seq analysis and found that differentially expressed genes (DEGs) associated with neuroactive ligand-receptor interaction, including genes related to GABA receptors, significantly changed after mice were treated with CRS. Targeted metabolomics analysis and enzyme-linked immunosorbent assay (ELISA) also showed that GABA levels in back skin tissues and serum significantly elevated in the CRS group. Notably, CRS-induced hair growth inhibition got aggravated by GABA and alleviated through GABAA antagonists, such as picrotoxin and ginkgolide A. RNA Sequencing analysis revealed that DEGs related to the cell cycle, DNA replication, purine metabolism, and pyrimidine metabolism pathways were significantly downregulated in dermal papilla (DP) cells after GABA treatment. Moreover, ginkgolide A, a GABAA antagonist extracted from the leaves of Ginkgo biloba, promoted the cell cycle of DP cells. Therefore, the present study demonstrated that the increase in GABA could promote CRS-induced hair growth inhibition by downregulating the cell cycle of DP cells and suggested that ginkgolide A may be a promising therapeutic drug for hair loss.

Keywords

Chronic restraint stress; Ginkgolide A; Hair follicle; Hair growth inhibition; γ-Aminobutyric acid.

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