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电针通过靶向组蛋白去乙酰化酶(HDAC)过表达和脑源性神经营养因子(BDNF)相关的Akt/糖原合成酶激酶-3β(GSK-3β)信号通路来改善创伤性脑损伤(TBI)功能障碍。

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

作者信息

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

机构信息

Graduate Institute of Acupuncture Science, China Medical University, Taichung, Taiwan.

Division of Colorectal Surgery, China Medical University Hospital, Taichung, Taiwan.

出版信息

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

DOI:10.3389/fncel.2022.880267
PMID:36016833
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9396337/
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.

摘要

背景

针刺或电针似乎是急性临床创伤性脑损伤(TBI)的一种潜在治疗方法;然而,针刺是否会影响TBI后的组蛋白去乙酰化酶(HDAC)表达或影响其他生化/神经生物学事件仍不确定。

材料与方法

我们使用行为测试、蛋白质免疫印迹法和免疫组织化学分析,来评估电针双侧合谷穴(LI4)和曲池穴(LI11)对重物坠落撞击加速(WD)和控制性皮质撞击(CCI)诱导的TBI模型的细胞和分子影响。

结果

WD和CCI诱导的TBI均导致行为功能障碍,增加皮质HDAC1和HDAC3亚型水平,激活小胶质细胞和星形胶质细胞,并降低皮质脑源性神经营养因子(BDNF)水平及其下游介质磷酸化Akt和磷酸化糖原合成酶激酶3β(phosphorylated-GSK-3β)水平。电针治疗可逆转运动、感觉运动以及学习/记忆缺陷。电针还可恢复HDAC1和HDAC3的过表达,并恢复TBI小鼠皮质中BDNF相关信号的下调。

结论

结果强烈表明,针刺对TBI相关的不良行为和生化影响具有多种益处,其潜在机制可能是通过靶向HDAC过表达和异常的BDNF相关Akt/GSK-3信号传导介导的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1e6/9396337/4b5be3db35b4/fncel-16-880267-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1e6/9396337/f8c8935d74a9/fncel-16-880267-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1e6/9396337/580237b8139e/fncel-16-880267-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1e6/9396337/2132a21cafcb/fncel-16-880267-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1e6/9396337/0759005a6f01/fncel-16-880267-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1e6/9396337/9b0f5310368a/fncel-16-880267-g008.jpg
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