Acupuncture inhibits NLRP3 inflammasome activation in the prefrontal cortex of a chronic stress rat model of depression. Issue 11 (12th October 2021)

• Record Type: Journal Article
• Authors: Li, Xiaoyan; Wang, Hongmei; Li, Chen; Wu, Jihong; Lu, Jun; Guo, Jian‐You; Tu, Ya
• Is Part Of: Anatomical record. Volume 304:Issue 11(2021)
• Page Start: 2470
• Page End: 2479
• Publication Date: 2021-10-12
• Subjects: acupuncture -- chronic unpredictable stress -- depression -- inflammation -- NLRP3 inflammasome; Anatomy -- Periodicals; Evolution (Biology) -- Periodicals; Morphology -- Periodicals; 571.3
• DOI: 10.1002/ar.24778
• Languages: English
• ISSNs: 1932-8486

Abstract

Abstract: The Nod‐like receptor family pyrin domain‐containing 3 (NLRP3) inflammasome‐driven inflammatory response plays a key role in the pathophysiology of depression. Mounting evidence suggests that acupuncture is an effective treatment for depression. In this study, we investigated the effects of acupuncture treatment at the acupoints Baihui (GV20) and Yintang (GV29) on NLRP3 inflammasome in the prefrontal cortex (PFC) of an animal model of depression. Rats that underwent chronic unpredictable mild stress (CUMS) for 6 weeks showed depressive‐like behaviors, which were confirmed by sucrose preference and locomotor activity in the open field test. The protein levels of NLRP3, apoptotic speck‐containing protein with a card (ASC), and cysteinyl aspartate specific proteinase‐1 (Caspase‐1) in the PFC were detected by Western blot analysis. The mRNA and protein expressions of interleukin‐1β (IL‐1β) and interleukin‐18 (IL‐18) in the PFC were measured by the real‐time polymerase chain reaction (RT‐PCR) and enzyme‐linked immunosorbent assay (ELISA), respectively. Our results showed that the depressive‐like behaviors in stressed rats were reversed by acupuncture treatment. Compared with control rats, the protein expression of NLRP3, ASC, and Caspase‐1 and the mRNA and protein expressions of IL‐1β and IL‐18 in the PFC were markedly increased in CUMS rats. Acupuncture treatment significantly decreased the levels of NLRP3 inflammasome components and inflammatory cytokines in the PFC. Acupuncture treatment also reduced the number of TUNEL‐positive cells in the PFC. These results suggested that acupuncture has antidepressant‐like effects, and its mechanism appears to be involved in the inhibition of NLRP3 inflammasome activation and apoptosis in the PFC. Chinese Abstract: NOD 样受体家族含 pyrin 结构域蛋白 3(NLRP3) 炎症小体在抑郁症的病理过程中起着重要作用。越来越多的研究表明针刺是治疗抑郁症的有效方法。在本实验中，我们研究了针刺百会 (GV20) 和印堂 (GV29) 对抑郁大鼠前额叶皮层 NLRP3 炎症小体的影响。采用 6 周慢性不可预知温和刺激方法建立抑郁大鼠模型，采用糖水偏好实验和旷场实验进行行为学检测。采用蛋白印迹法(Western blot) 检测大鼠前额叶皮层 NLRP3、凋亡相关的斑点样蛋白 (ASC)、半胱氨酸天冬氨酸蛋白酶‐1 (Caspase‐1) 的蛋白水平；采用实时荧光定量 PCR(RT‐PCR) 方法检测炎性细胞因子白细胞介素‐1β (IL‐1β) 和白细胞介素‐18(IL‐18) 的 mRNA 表达；采用酶联免疫吸附(ELISA)法检测IL‐1β 和IL‐18 的浓度; 采用 TUNEL 染色法检测前额叶皮层细胞凋亡。结果表明，针刺可逆转应激大鼠的抑郁样行为。与对照组相比， CUMS 大鼠前额叶皮层NLRP3，ASC，Caspase‐1 的蛋白表达、IL‐1β和IL‐18的基因和蛋白表达均显著增加。针刺治疗可显著降低抑郁大鼠前额叶皮层 NLRP3 炎症小体成分和促炎性细胞因子的水平。针刺治疗也减少了抑郁大鼠前额叶皮层 TUNEL 阳性细胞的数量。这些结果表明，针刺具有抗抑郁作用，其机制可能与抑制前额叶皮层 NLRP3 炎症小体活化和凋亡有关。