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酒精干扰海马神经发生的机制及其修复策略

Mechanisms of Alcohol Interference with Hippocampal Neurogenesis and its Repair Strategies.

作者信息

Wang Jinghan, Zhang Tianxiang, Gao Ziang, Liu Yue, Wei Ziyu, Wang Yanlong

机构信息

Lin He's Academician Workstation of New Medicine and Clinical Translation in Jining Medical University, Jining Medical University, Jining, Shandong Province, China.

Clinical Medical College, Jining Medical University, Jining, Shandong Province, China.

出版信息

Mol Neurobiol. 2025 Jul 17. doi: 10.1007/s12035-025-05240-6.

Abstract

The hippocampus is the central target of alcohol-induced neurotoxicity in impairing memory function, with neurogenesis inhibition being its primary mechanism of action. Alcohol interference with hippocampal neurogenesis is closely associated with various diseases. However, limited treatment options currently exist for alcohol-induced hippocampal neuronal damage, and the therapeutic effects are unsatisfactory, placing a significant economic and mental burden on patients' families and society. This review summarises the effects of alcohol on hippocampal neurogenesis during the foetal, adolescent, and adult periods, as well as its mechanisms of action. During the foetal period, alcohol exposure may lead to a decrease in hippocampal cell numbers, impairment of hippocampal synaptic plasticity, alterations in neurodevelopmental proteins, reduced expression of various receptors, interference with neural stem cell differentiation, changes in hippocampal DNA methylation, modifications in neurotrophic factor levels, induction of neuroinflammatory responses, and slow ethanol metabolism. In adolescence, alcohol consumption can adversely affect hippocampal neurogenesis and synapse formation, disrupt metabolic processes within the hippocampus, trigger inflammatory responses, and impair the synthesis of neurotrophic factors. During adulthood, alcohol intake may lead to a reduction in hippocampal neurogenesis, and provoke neuroinflammatory responses, suppress the expression of neurotrophic factors, alter hippocampal metabolite levels, and impact cytoskeletal dynamics within the hippocampus. We also explore potential repair strategies, including pharmacological treatments, nutritional supplementation, plant extracts, and physical therapy, to promote more effective therapeutic approaches.

摘要

海马体是酒精诱导神经毒性损害记忆功能的主要靶点,神经发生抑制是其主要作用机制。酒精对海马体神经发生的干扰与多种疾病密切相关。然而,目前针对酒精诱导的海马体神经元损伤的治疗选择有限,治疗效果也不尽人意,给患者家庭和社会带来了巨大的经济和精神负担。本综述总结了酒精在胎儿期、青少年期和成年期对海马体神经发生的影响及其作用机制。在胎儿期,酒精暴露可能导致海马体细胞数量减少、海马体突触可塑性受损、神经发育蛋白改变、各种受体表达降低、神经干细胞分化受干扰、海马体DNA甲基化变化、神经营养因子水平改变、神经炎症反应诱导以及乙醇代谢缓慢。在青少年期,饮酒会对海马体神经发生和突触形成产生不利影响,扰乱海马体内的代谢过程,引发炎症反应,并损害神经营养因子的合成。在成年期,饮酒可能导致海马体神经发生减少,引发神经炎症反应,抑制神经营养因子的表达,改变海马体代谢物水平,并影响海马体内的细胞骨架动力学。我们还探讨了潜在的修复策略,包括药物治疗、营养补充、植物提取物和物理治疗,以促进更有效的治疗方法。

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