脊髓
下调和上调
神经病理性疼痛
脑源性神经营养因子
神经营养因子
痛觉过敏
神经科学
葛兰素史克-3
慢性疼痛
微量注射
医学
内科学
小发夹RNA
内分泌学
心理学
伤害
激酶
化学
生物
细胞生物学
基因敲除
受体
生物化学
基因
细胞凋亡
作者
Shuxia Zhang,Yeru Chen,Yongjie Wang,Hongwei Wang,Dandan Yao,Gang Chen
标识
DOI:10.1007/s12264-023-01152-4
摘要
Abstract Microtubule-associated protein Tau is responsible for the stabilization of neuronal microtubules under normal physiological conditions. Much attention has been focused on Tau’s contribution to cognition, but little research has explored its role in emotions such as pain, anxiety, and depression. In the current study, we found a significant increase in the levels of p-Tau (Thr231), total Tau, IL-1β, and brain-derived neurotrophic factor (BDNF) on day 7 after complete Freund's adjuvant (CFA) injection; they were present in the vast majority of neurons in the spinal dorsal horn. Microinjection of Mapt -shRNA recombinant adeno-associated virus into the spinal dorsal cord alleviated CFA-induced inflammatory pain and inhibited CFA-induced IL-1β and BDNF upregulation. Importantly, Tau overexpression was sufficient to induce hyperalgesia by increasing the expression of IL-1β and BDNF. Furthermore, the activation of glycogen synthase kinase 3 beta partly contributed to Tau accumulation. These findings suggest that Tau in the dorsal horn could be a promising target for chronic inflammatory pain therapy.
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