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.

中文翻译：

---

脊髓中 Tau 蛋白的积累通过上调 IL-1β 和 BDNF 导致慢性炎症性疼痛

摘要

微管相关蛋白 Tau 负责正常生理条件下神经元微管的稳定。很多注意力都集中在 Tau 对认知的贡献上，但很少有研究探讨它在疼痛、焦虑和抑郁等情绪中的作用。在本研究中，我们发现注射完全弗氏佐剂（CFA）后第7天，p-Tau（Thr231）、总Tau、IL-1β和脑源性神经营养因子（BDNF）的水平显着增加；它们存在于脊髓背角的绝大多数神经元中。将Mapt -shRNA重组腺相关病毒显微注射到脊髓中可减轻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 过度表达足以通过增加 IL-1β 和 BDNF 的表达来诱导痛觉过敏。此外，糖原合成酶激酶 3 beta 的激活部分促进了 Tau 的积累。这些发现表明，背角中的 Tau 蛋白可能是慢性炎症疼痛治疗的一个有希望的靶点。