Lv Hao, Gao Ziang, Wang Yunfei, Chen Siyuan, Liu Peiqiang, Xie Yulie, Guan Mengting, Cong Jianchao, Xu Yu
Department of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, 238 Jiefang Rd, Wuhan, Hubei, 430060, China.
Department of Rhinology and Allergy, Renmin Hospital of Wuhan University, 238 Jiefang Rd, Wuhan, Hubei, 430060, China.
Neurochem Res. 2023 Dec;48(12):3639-3651. doi: 10.1007/s11064-023-04012-9. Epub 2023 Aug 14.
Allergic rhinitis (AR) is a widespread disease that is frequently comorbid with depression. However, the mechanisms and treatments for depression in AR remain underexplored. Metformin, a widely used antidiabetic drug, has shown antidepressant effects. The aim of this study was to explore the effects and potential mechanisms of metformin on depression-like behaviors in an AR mouse model. In the present study, mice were sensitized and challenged with ovalbumin (OVA) to induce AR. Results showed that mice with AR exhibited significant depression-like behavior which was attenuated by metformin. In addition, the levels of expression of synaptic plasticity markers (anti-microtubule-associated protein 2, synaptophysin, postsynaptic density protein 95), neurogenesis markers (doublecortin and Ki-67), and brain-derived neurotrophic factor were decreased in the olfactory bulb (OB) of mice with AR, while metformin ameliorated all these alterations and reduced apoptosis in the OB of these mice. Furthermore, it enhanced the phosphorylation of AMP-activated kinase (AMPK) and the levels of ten-eleven translocation 2 (TET2) and 5-hydroxymethylcytosine in the OB. In conclusion, our findings suggest that metformin might be a viable strategy for treating AR-related depression, possibly by modulating neuroplasticity, neurogenesis, apoptosis, and BDNF signaling in the OB via the AMPK/TET2 pathway.
变应性鼻炎（AR）是一种常见疾病，常与抑郁症共病。然而，AR中抑郁症的发病机制和治疗方法仍未得到充分探索。二甲双胍是一种广泛使用的抗糖尿病药物，已显示出抗抑郁作用。本研究的目的是探讨二甲双胍对AR小鼠模型中抑郁样行为的影响及潜在机制。在本研究中，用卵清蛋白（OVA）对小鼠进行致敏和激发以诱导AR。结果显示，患有AR的小鼠表现出显著的抑郁样行为，而二甲双胍可使其减轻。此外，突触可塑性标志物（抗微管相关蛋白2、突触素、突触后致密蛋白95）、神经发生标志物（双皮质素和Ki-67）以及脑源性神经营养因子的表达水平在患有AR的小鼠嗅球（OB）中降低，而二甲双胍改善了所有这些改变，并减少了这些小鼠OB中的细胞凋亡。此外，它增强了OB中AMP激活蛋白激酶（AMPK）的磷酸化以及10-11易位蛋白2（TET2）和5-羟甲基胞嘧啶的水平。总之，我们的研究结果表明，二甲双胍可能是治疗AR相关抑郁症的一种可行策略，可能是通过AMPK/TET2途径调节OB中的神经可塑性、神经发生、细胞凋亡和BDNF信号传导来实现的。
