Electroacupuncture improves TBI dysfunction by targeting HDAC overexpression and BDNF-associated Akt/GSK-3β signaling

Shih-Ya Hung; Hsin-Yi Chung; Sih-Ting Luo; Yu-Ting Chu; Yu-Hsin Chen; Iona J MacDonald; Szu-Yu Chien; Peddanna Kotha; Liang-Yo Yang; Ling-Ling Hwang; Nae J Dun; De-Maw Chuang; Yi-Hung Chen

doi:10.3389/fncel.2022.880267

Electroacupuncture improves TBI dysfunction by targeting HDAC overexpression and BDNF-associated Akt/GSK-3β signaling

Front Cell Neurosci. 2022 Aug 9:16:880267. doi: 10.3389/fncel.2022.880267. eCollection 2022.

Authors

Shih-Ya Hung^{1

2}, Hsin-Yi Chung¹, Sih-Ting Luo¹, Yu-Ting Chu¹, Yu-Hsin Chen³, Iona J MacDonald¹, Szu-Yu Chien¹, Peddanna Kotha¹, Liang-Yo Yang^{4

5}, Ling-Ling Hwang³, Nae J Dun⁶, De-Maw Chuang⁷, Yi-Hung Chen^{1

8

9}

Affiliations

¹ Graduate Institute of Acupuncture Science, China Medical University, Taichung, Taiwan.
² Division of Colorectal Surgery, China Medical University Hospital, Taichung, Taiwan.
³ Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan.
⁴ Department of Physiology, School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan.
⁵ Laboratory for Neural Repair, China Medical University Hospital, Taichung, Taiwan.
⁶ Department of Pharmacology, Temple University School of Medicine, Philadelphia, PA, United States.
⁷ Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, United States.
⁸ Chinese Medicine Research Center, China Medical University, Taichung, Taiwan.
⁹ Department of Photonics and Communication Engineering, Asia University, Taichung, Taiwan.

Abstract

Background: Acupuncture or electroacupuncture (EA) appears to be a potential treatment in acute clinical traumatic brain injury (TBI); however, it remains uncertain whether acupuncture affects post-TBI histone deacetylase (HDAC) expression or impacts other biochemical/neurobiological events.

Materials and methods: We used behavioral testing, Western blot, and immunohistochemistry analysis to evaluate the cellular and molecular effects of EA at LI4 and LI11 in both weight drop-impact acceleration (WD)- and controlled cortical impact (CCI)-induced TBI models.

Results: Both WD- and CCI-induced TBI caused behavioral dysfunction, increased cortical levels of HDAC1 and HDAC3 isoforms, activated microglia and astrocytes, and decreased cortical levels of BDNF as well as its downstream mediators phosphorylated-Akt and phosphorylated-GSK-3β. Application of EA reversed motor, sensorimotor, and learning/memory deficits. EA also restored overexpression of HDAC1 and HDAC3, and recovered downregulation of BDNF-associated signaling in the cortex of TBI mice.

Conclusion: The results strongly suggest that acupuncture has multiple benefits against TBI-associated adverse behavioral and biochemical effects and that the underlying mechanisms are likely mediated by targeting HDAC overexpression and aberrant BDNF-associated Akt/GSK-3 signaling.

Keywords: Akt/GSK-3β; BDNF; electroacupuncture; histone deacetylases; motor function tests; preclinical traumatic brain injury.