Effects of food-borne cholesterol supplementation on lead-induced neurodevelopmental impairments of rats based on BDNF signaling pathway and cholesterol metabolism

作者：Susu Wang, An-Xin Lu, Wan-He Li, Hong Zhang, Chunping Hu, Junxia Liu, Hui Pan, Meiqin Wu, Xi Xu, Chonghuai Yan, Zhenyan Gao · 发表于：Ecotoxicology and Environmental Safety · 年份：2023 · DOI：10.1016/j.ecoenv.2023.115026 · 被引用次数：10 · 研究领域：Heavy Metal Exposure and Toxicity、Trace Elements in Health、Mercury impact and mitigation studies

Despite the ubiquity and prevalence of lead (Pb) in the environment and industry, the mechanism of lead-induced neurotoxicity in the brain remains unclear, let alone its prevention and treatment. In this study, we hypothesized that exogenous cholesterol supplementation acts as an effective remedy for lead-induced neurodevelopmental impairments caused by lead. Forty 21-day-old male rats were randomly divided into four groups and administered 0.1 % lead water and/or 2 % cholesterol-containing feed for 30 d. Ultimately, rats in the lead group lost weight, accompanied by spatial learning and memory impairments as verified by the Morris water maze test, in which the escape latency of rats was prolonged, and the number of crossings in the target platform and the residence time in the target quadrant were significantly diminished compared to the control group. Hematoxylin-Eosin (H&E) staining and Nissl staining illustrated that typical pathological morphology occurred in the brain tissue of the lead group, where the tissue structure was loose, the number of hippocampal neurons and granulosa cells decreased significantly and were arranged loosely, along with enlarged intercellular space, light matrix staining, and decline in Nissl bodies. In addition, inflammatory response and oxidative stress were significantly induced by lead. Immunofluorescence experiments showed apparent activation of astrocytes and microglia, followed by the enhancement of TNF-α and IL-β levels. Moreover, the MD...