浙江大学Gang Chen研究组发现，脊髓中的Tau积累通过上调IL-1β和BDNF导致慢性炎症性疼痛。2023年12月26日，《神经科学通报》在线发表了这项成果。

研究人员发现在注射完全弗氏佐剂（CFA）后的第7天，p-Tau（Thr231）、总Tau、IL-1β和脑源性神经营养因子（BDNF）的水平显著增加；它们出现在脊髓背角的绝大多数神经元中。向脊髓背索微量注射Mapt-shRNA重组腺相关病毒可减轻CFA诱导的炎性疼痛，并抑制CFA诱导的IL-1β和BDNF上调。

重要的是，Tau的过表达足以通过增加IL-1β和BDNF的表达来诱导痛觉减退。此外，糖原合酶激酶3β的激活也在一定程度上促进了Tau的积累。这些研究结果表明，背角的Tau可能是治疗慢性炎症性疼痛的一个很有前景的靶点。

据悉，在正常生理条件下，微管相关蛋白Tau负责稳定神经元微管。Tau对认知的贡献一直备受关注，但很少有研究探讨它在疼痛、焦虑和抑郁等情绪中的作用。

附：英文原文

Title: Tau Accumulation in the Spinal Cord Contributes to Chronic Inflammatory Pain by Upregulation of IL-1β and BDNF

Author: Zhang, Shuxia, Chen, Yeru, Wang, Yongjie, Wang, Hongwei, Yao, Dandan, Chen, Gang

Issue&Volume: 2023-12-26

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.

DOI: 10.1007/s12264-023-01152-4

Source: https://link.springer.com/article/10.1007/s12264-023-01152-4