Key Laboratory of Occupational Environment and Health, Guangzhou Occupational Disease Prevention and Treatment Hospital, Guangzhou, China; Institute of Occupational and Environmental Health, Guangzhou Medical University, Guangzhou, China.
School of Public Health, Guangzhou Medical University, Guangzhou, China.
Ecotoxicol Environ Saf. 2024 Nov 1;286:117183. doi: 10.1016/j.ecoenv.2024.117183. Epub 2024 Oct 22.
Noise pollution pervades daily working and living environment, becoming a serious public health problem. In addition to causing auditory impairment, noise independently contributes to cognitive decline as a risk factor. Though neuroinflammation plays an important role in noise-induced cognitive deficits, the mechanisms underlying noise-induced neuroinflammation in the hippocampus are still poorly understood. Glial hyperactivation of the NLRP3 inflammasome contributes to various neurodegenerative diseases, including Alzheimer's disease (AD) and Parkinson's disease (PD). However, whether the NLRP3 inflammasome plays a role in noise-induced cognitive impairment remains to be further investigated.
Adult male Wistar rats were exposed to 100 dB white noise (4 h/day) for 30 days with or without injection of the NLRP3 inhibitor MCC950 (10 mg/kg/day). The Morris water maze (MWM) test and the open field test (OFT) were performed to evaluate learning and memory ability of rats. HE staining was used to explore hippocampal pathological changes, while immunohistochemical staining was employed to evaluate the number and morphology of microglia and astrocytes. The mRNA levels of the NLRP3 inflammasome in the hippocampus were examined by Real-time PCR. The protein levels of NLRP3 inflammasome, inflammatory cytokines, p-Tau-S396, and amyloid-β (Aβ) 42 in the hippocampus were examined by Western blot. Immunofluorescence was used to observe the distribution of NLRP3 in glial cells and neurons, and the assembly of the NLRP3 inflammasome.
We found that noise exposure induced learning and memory impairment in rats, mainly related to the activation of microglia and astrocytes in hippocampus region. Noise exposure increased the protein levels of p-Tau-S396, Aβ42, ionized calcium binding adapter molecule 1 (Iba-1), glial fibrillary acidic protein (GFAP), interleukin (IL)-1β, IL-18, and tumor necrosis factor-α (TNF-α) in hippocampus. Furthermore, the hippocampus of noise-exposed rats showed elevated protein levels of NLRP3, ASC and cleaved caspase-1. The co-labeled immunofluorescence levels of Iba-1 or GFAP with NLRP3 significantly increased in the dentate gyrus (DG) region of the hippocampus. NLRP3 inhibitor MCC950 intervention reversed chronic noise-induced activation of NLRP3 inflammasome, AD-like pathologies and impairment of learning and memory in rats.
The NLRP3 inflammasome-mediated neuroinflammation played an essential role in chronic noise-induced cognitive dysfunction. These results provide novel strategies for the prevention and treatment of cognitive deficits caused by chronic noise.
噪声污染普遍存在于日常工作和生活环境中，成为严重的公共卫生问题。除了导致听力损伤外，噪声作为一个风险因素，独立导致认知能力下降。尽管神经炎症在噪声引起的认知缺陷中起着重要作用，但噪声引起海马体神经炎症的机制仍知之甚少。NLRP3 炎性小体的神经胶质过度激活与各种神经退行性疾病有关，包括阿尔茨海默病（AD）和帕金森病（PD）。然而，NLRP3 炎性小体是否在噪声引起的认知障碍中发挥作用仍有待进一步研究。
成年雄性 Wistar 大鼠暴露于 100dB 白噪声（每天 4 小时）30 天，同时或不注射 NLRP3 抑制剂 MCC950（每天 10mg/kg）。通过 Morris 水迷宫（MWM）测试和旷场测试（OFT）评估大鼠的学习和记忆能力。HE 染色用于探索海马体的病理变化，免疫组织化学染色用于评估小胶质细胞和星形胶质细胞的数量和形态。通过实时 PCR 检测海马体 NLRP3 炎性小体的 mRNA 水平。通过 Western blot 检测海马体 NLRP3 炎性小体、炎性细胞因子、p-Tau-S396 和淀粉样β（Aβ）42 的蛋白水平。免疫荧光用于观察 NLRP3 在神经胶质细胞和神经元中的分布以及 NLRP3 炎性小体的组装。
我们发现，噪声暴露会导致大鼠学习和记忆能力受损，主要与海马区小胶质细胞和星形胶质细胞的激活有关。噪声暴露增加了海马体中 p-Tau-S396、Aβ42、离子钙结合接头分子 1（Iba-1）、胶质纤维酸性蛋白（GFAP）、白细胞介素（IL）-1β、IL-18 和肿瘤坏死因子-α（TNF-α）的蛋白水平。此外，噪声暴露大鼠的海马体中 NLRP3、ASC 和切割半胱天冬酶-1 的蛋白水平升高。在海马体齿状回（DG）区域，与 Iba-1 或 GFAP 共标记的免疫荧光水平明显增加。NLRP3 抑制剂 MCC950 干预逆转了慢性噪声诱导的 NLRP3 炎性小体激活、AD 样病理和大鼠学习记忆损伤。
NLRP3 炎性小体介导的神经炎症在慢性噪声诱导的认知功能障碍中起着重要作用。这些结果为预防和治疗慢性噪声引起的认知缺陷提供了新的策略。
