Shanxi Medical University Fenyang College, China; Pathology Department, Shanxi Fenyang Hospital, China.
Shanxi Medical University Fenyang College, China; Pathology Department, Shanxi Fenyang Hospital, China.
Environ Pollut. 2024 Dec 1;362:124973. doi: 10.1016/j.envpol.2024.124973. Epub 2024 Sep 20.
Aluminium exposure has been found to impair learning and memory abilities; however, the underlying molecular mechanisms remain unclear. In this study we conducted a double luciferase reporter assay to determine whether miR-351-5p regulates cytoplasmic polyadenylation element binding protein (CPEB) 3 mRNA. To this end, we overexpressed and inhibited miR-351-5p via stereotaxic microinjections of adeno-associated virus (AAV) into the hippocampus of Sprague Dawley rats in a sub-chronic aluminium exposure model to examine learning and memory ability using Morris water maze. Ultrastructural electron microscopy and Golgi staining were used to examine morphological changes in hippocampal neurons. In addition, we examined the levels of synaptic plasticity-related proteins (PRPs) and CPEB3 to determine the involvement of the miR-351-5P/CPEB3/PRPs pathway in aluminium neurotoxicity. Sub-chronic aluminium exposure reduced the spatial learning and memory ability of rats. Overexpression of AAV-miR-351-5P in the hippocampus aggravated the impairment of spatial learning and memory abilities of aluminium-treated rats, whereas inhibition of AAV-miR-351-5p expression alleviated it. Western blotting suggested that sub-chronic aluminium exposure increased miR-351-5p levels and reduced the expression of CPEB3 and PRPs in the hippocampus. Treatment with an AAV-miR-351-5p inhibitor partially recovered CPEB3 and PRPs. Double luciferase reporter assay results showed that CPEB3 was a direct target of miR-351-5p, while electron microscopy suggested that aluminium could damage mitochondria and synapses in the CA1 of the hippocampus. Golgi staining results indicated that aluminium could reduce the number of dendritic spines in hippocampal neurons. Inhibition of miR-351-5p restored the synaptic structure and growth of dendritic spines in the hippocampus. The involvement of the miR-351-5P/CPEB3/RPPs pathway in aluminium neurotoxicity was confirmed. Our findings suggest that inhibition of miR-351-5p can alleviate learning and memory impairments by increasing CPEB3 and PRPs.
铝暴露已被发现会损害学习和记忆能力；然而，其潜在的分子机制尚不清楚。在这项研究中，我们通过立体定位微注射腺相关病毒（AAV）到慢性铝暴露模型的 Sprague Dawley 大鼠海马中来进行双荧光素酶报告基因检测，以确定 miR-351-5p 是否调节细胞质多聚腺苷酸化元件结合蛋白（CPEB）3 mRNA。为此，我们通过立体定位微注射腺相关病毒（AAV）到慢性铝暴露模型的 Sprague Dawley 大鼠海马中来过表达和抑制 miR-351-5p，使用 Morris 水迷宫来检查学习和记忆能力。超微结构电子显微镜和高尔基染色用于检查海马神经元的形态变化。此外，我们还检查了突触可塑性相关蛋白（PRPs）和 CPEB3 的水平，以确定 miR-351-5P/CPEB3/PRPs 通路是否参与铝神经毒性。慢性铝暴露降低了大鼠的空间学习和记忆能力。海马中过表达 AAV-miR-351-5P 加重了铝处理大鼠空间学习和记忆能力的损伤，而抑制 AAV-miR-351-5p 的表达则减轻了损伤。Western blot 表明，慢性铝暴露增加了 miR-351-5p 的水平，降低了海马中 CPEB3 和 PRPs 的表达。用 AAV-miR-351-5p 抑制剂处理可部分恢复 CPEB3 和 PRPs。双荧光素酶报告基因检测结果表明 CPEB3 是 miR-351-5p 的直接靶标，而电子显微镜表明铝可以损伤海马 CA1 区的线粒体和突触。高尔基染色结果表明，铝可以减少海马神经元树突棘的数量。抑制 miR-351-5p 可恢复海马中的突触结构和树突棘的生长。miR-351-5P/CPEB3/RPPs 通路在铝神经毒性中的作用得到了证实。我们的研究结果表明，抑制 miR-351-5p 可以通过增加 CPEB3 和 PRPs 来减轻学习和记忆障碍。
