Wang Yunfei, Xie Yulie, Liu Peiqiang, Lv Hao, Guan Mengting, Cong Jianchao, Wang Yan, Xu Yu
Department of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, China.
Department of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, China.
Neuroscience. 2025 Apr 6;571:52-61. doi: 10.1016/j.neuroscience.2025.01.043. Epub 2025 Jan 21.
In addition to nasal symptoms, allergic rhinitis (AR) has increasingly been reported to be associated with depression-like behaviors. Recent evidence suggests that neuroinflammation in the hypothalamus may cause these depressive symptoms in AR. However, the precise mechanisms and effective treatments remain to be elucidated. This study investigated the ameliorative effects of metformin on neuroinflammation in the hypothalamus, depressive-like behavior and the underlying molecular mechanisms of AR mice. Mice were administered ovalbumin (OVA) intranasally to induce allergic rhinitis and subsequently subjected to behavioral experiments to detect depressive-like behavior. The roles of the TRPV1/NLRP3 pathway in depression-like behaviors in AR were examined in vivo. Additionally, the mechanism of TRPV1/NLRP3-mediated neuroinflammation was investigated in vitro. Finally, metformin was utilized to explore its possible mechanisms and efficacy in treating depressive-like behavior in AR. AR mice exhibited significant depressive-like behavior, which was attenuated by metformin. The number of Iba-1 microglia significantly increased in the hypothalamus of AR mice. The expression of NLRP3 was significantly upregulated in the hypothalamus, activating microglia. Metformin ameliorated the neuropsychiatric symptoms by reducing NLRP3 expression in the hypothalamus. Moreover, metformin inhibited LPS-induced upregulation of the TRPV1/NLRP3 signaling pathway in microglial cell line, an effect that can be reversed by the TRPV1-specific agonist capsaicin. Increased TRPV1 expression activates the NLRP3 inflammasome in hypothalamic microglia, promoting the pathological process of depressive-like behavior in AR mice. Metformin could effectively treat neuroinflammation by regulating microglia via TRPV1 downregulation, indicating its potential as a treatment for depressive-like behaviors in AR.
除鼻部症状外，越来越多的报道表明过敏性鼻炎（AR）与抑郁样行为有关。最近的证据表明，下丘脑的神经炎症可能导致AR患者出现这些抑郁症状。然而，确切的机制和有效治疗方法仍有待阐明。本研究探讨了二甲双胍对AR小鼠下丘脑神经炎症、抑郁样行为及其潜在分子机制的改善作用。通过鼻内给予小鼠卵清蛋白（OVA）诱导过敏性鼻炎，随后进行行为实验以检测抑郁样行为。在体内研究了TRPV1/NLRP3通路在AR抑郁样行为中的作用。此外，在体外研究了TRPV1/NLRP3介导的神经炎症机制。最后，利用二甲双胍探索其治疗AR抑郁样行为的可能机制和疗效。AR小鼠表现出明显的抑郁样行为，而二甲双胍可使其减轻。AR小鼠下丘脑Iba-1小胶质细胞数量显著增加。下丘脑NLRP3表达显著上调，激活小胶质细胞。二甲双胍通过降低下丘脑NLRP3表达改善神经精神症状。此外，二甲双胍抑制小胶质细胞系中LPS诱导的TRPV1/NLRP3信号通路上调，TRPV1特异性激动剂辣椒素可逆转这一作用。TRPV1表达增加激活下丘脑小胶质细胞中的NLRP3炎性小体，促进AR小鼠抑郁样行为的病理过程。二甲双胍可通过下调TRPV1调节小胶质细胞，有效治疗神经炎症，表明其在治疗AR抑郁样行为方面具有潜力。
