Department of Maternal, Child and Adolescent Health, School of Public Health, Shenyang Medical College, Liaoning Province 110034, Shenyang, People's Republic of China.
Department of Shenyang Maternity and Child Health Hospital, Shenyang, Liaoning Province, 110034, People's Republic of China.
Biol Trace Elem Res. 2024 Aug;202(8):3740-3749. doi: 10.1007/s12011-023-03961-0. Epub 2023 Nov 20.
Aluminum is a common environmental neurotoxin. Aluminum ions can cross the blood-brain barrier and accumulate in different brain regions, damage brain tissue, and cause cognitive impairment, but the molecular mechanism of aluminum neurotoxicity is not precise. This study investigated the effects of miR-204-5p, target gene EphB2, and downstream signaling pathway NMDAR-ERK-CREB-Arc on cognitive dysfunction induced by aluminum exposure. The results showed that the learning and memory of the rats were impaired in behavior. The accumulation of aluminum in the hippocampus resulted in the damage of nerve cell morphology in the CA1 region of the hippocampus. The expression level of miR-204-5p was increased, and the mRNA and protein expressions of EphB2, NMDAR2B, ERK1/2, CREB, and Arc were decreased. The results indicated that the mechanism of impaired learning and memory induced by aluminum exposure might promote the expression of miR-204-5P and further inhibit the expression of the target gene EphB2 and its downstream signaling pathway NMDAR-ERK-CREB-Arc.
铝是一种常见的环境神经毒素。铝离子可以穿过血脑屏障并在不同的脑区积累，损害脑组织并导致认知障碍，但铝神经毒性的分子机制尚不清楚。本研究探讨了 miR-204-5p、靶基因 EphB2 及其下游信号通路 NMDAR-ERK-CREB-Arc 对铝暴露引起的认知功能障碍的影响。结果表明，铝暴露导致大鼠的学习和记忆能力受损。铝在海马体中的积累导致海马体 CA1 区神经细胞形态受损。miR-204-5p 的表达水平升高，EphB2、NMDAR2B、ERK1/2、CREB 和 Arc 的 mRNA 和蛋白表达降低。结果表明，铝暴露引起的学习和记忆受损的机制可能促进 miR-204-5P 的表达，进而抑制靶基因 EphB2 及其下游信号通路 NMDAR-ERK-CREB-Arc 的表达。
