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

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

Research output: Contribution to journal › Article › peer-review

4 Citations (Scopus)

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.

Original language	English
Pages (from-to)	880267
Journal	Frontiers in Cellular Neuroscience
Volume	16
DOIs	https://doi.org/10.3389/fncel.2022.880267
Publication status	Published - 2022

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Hung, S.-Y., Chung, H.-Y., Luo, S.-T., Chu, Y.-T., Chen, Y.-H., MacDonald, I. J., Chien, S.-Y., Kotha, P., Yang, L.-Y., Hwang, L.-L., Dun, N. J., Chuang, D.-M., & Chen, Y.-H. (2022). Electroacupuncture improves TBI dysfunction by targeting HDAC overexpression and BDNF-associated Akt/GSK-3β signaling. Frontiers in Cellular Neuroscience, 16, 880267. https://doi.org/10.3389/fncel.2022.880267

Hung, S-Y, Chung, H-Y, Luo, S-T, Chu, Y-T, Chen, Y-H, MacDonald, IJ, Chien, S-Y, Kotha, P, Yang, L-Y, Hwang, L-L, Dun, NJ, Chuang, D-M & Chen, Y-H 2022, 'Electroacupuncture improves TBI dysfunction by targeting HDAC overexpression and BDNF-associated Akt/GSK-3β signaling', Frontiers in Cellular Neuroscience, vol. 16, pp. 880267. https://doi.org/10.3389/fncel.2022.880267

@article{7b8460d329fe4675bd7adb9c19261e02,

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

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.",

author = "Shih-Ya Hung and Hsin-Yi Chung and Sih-Ting Luo and Yu-Ting Chu and Yu-Hsin Chen and MacDonald, {Iona J} and Szu-Yu Chien and Peddanna Kotha and Liang-Yo Yang and Ling-Ling Hwang and Dun, {Nae J} and De-Maw Chuang and Yi-Hung Chen",

note = "Copyright {\textcopyright} 2022 Hung, Chung, Luo, Chu, Chen, MacDonald, Chien, Kotha, Yang, Hwang, Dun, Chuang and Chen.",

year = "2022",

doi = "10.3389/fncel.2022.880267",

language = "English",

volume = "16",

pages = "880267",

journal = "Frontiers in Cellular Neuroscience",

issn = "1662-5102",

publisher = "Frontiers Media SA",

}

TY - JOUR

T1 - Electroacupuncture improves TBI dysfunction by targeting HDAC overexpression and BDNF-associated Akt/GSK-3β signaling

AU - Hung, Shih-Ya

AU - Chung, Hsin-Yi

AU - Luo, Sih-Ting

AU - Chu, Yu-Ting

AU - Chen, Yu-Hsin

AU - MacDonald, Iona J

AU - Chien, Szu-Yu

AU - Kotha, Peddanna

AU - Yang, Liang-Yo

AU - Hwang, Ling-Ling

AU - Dun, Nae J

AU - Chuang, De-Maw

AU - Chen, Yi-Hung

PY - 2022

Y1 - 2022

N2 - 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.

AB - 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.

U2 - 10.3389/fncel.2022.880267

DO - 10.3389/fncel.2022.880267

M3 - Article

C2 - 36016833

SN - 1662-5102

VL - 16

SP - 880267

JO - Frontiers in Cellular Neuroscience

JF - Frontiers in Cellular Neuroscience

ER -

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

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