Frontiers in Cellular Neuroscience (Aug 2022)

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

  • Shih-Ya Hung,
  • 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,
  • Liang-Yo Yang,
  • Ling-Ling Hwang,
  • Nae J. Dun,
  • De-Maw Chuang,
  • Yi-Hung Chen,
  • Yi-Hung Chen,
  • Yi-Hung Chen

DOI
https://doi.org/10.3389/fncel.2022.880267
Journal volume & issue
Vol. 16

Abstract

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BackgroundAcupuncture 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 methodsWe 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.ResultsBoth 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.ConclusionThe 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.

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