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胆碱磷酰丝氨酸对双重应激大鼠模型中非空间记忆和神经元分化的影响。

The effect of choline alphoscerate on non spatial memory and neuronal differentiation in a rat model of dual stress.

机构信息

Department of Biomedicine & Health Sciences, College of Medicine, The Catholic University of Korea, St. Mary's Hospital, Seoul, Republic of Korea.

Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, The Catholic University of Korea, Seoul St. Mary's Hospital, Seoul, Republic of Korea.

出版信息

Brain Res. 2022 Jul 1;1786:147900. doi: 10.1016/j.brainres.2022.147900. Epub 2022 Apr 6.

Abstract

Choline alphoscerate (α-GPC) is a choline-based compound and acetylcholine precursor commonly found in the brain; it has been known to be effective in treating neuronal injury and increasing the levels of acetylcholine (Ach) and brain-derived neurotrophic factor (BDNF) which in turn enhances memory and cognitive function. This study was designed to establish rat models of dual stress using noise and restraint in order to investigate the effect of α-GPC on cognitive function and neuronal differentiation after dual stress. The rats were randomly divided into four groups as follows: a control group (CG), a control with α-GPC group (CDG), a noise-restraint stress group (NRSG), and a noise-restraint stress with α-GPC group (NRSDG). Experimental groups were exposed to a 110 dB sound pressure level (SPL) white band noise and restraint at the same time for 3 h/day for 7 days. Alpha-GPC (400 mg/kg) was administered orally after stress exposure for 7 days. NRSG showed decreased memory function, increased stress hormone, hearing loss, and neuronal damage of the brain. In the hippocampus of NRSG, significantly increased expression of IL-1β and decreased expression of both choline acetyltransferase (ChAT) and BDNF were observed. On the contrary, NRSDG showed better memory function compared to NRSG, which indicates the neuroprotective effect of α-GPC. In addition, NRSDG showed decreased immune response and increased ChAT and BDNF expression as well as neuroblast expression in the hippocampus, which suggests that α-GPC enhances BDNF expression and protects the activity of immature cells in the hippocampus. To the best of our knowledge, this is the first study to show the protective effect of α-GPC on cognitive dysfunction by promotion of neuronal differentiation in an animal model of stress.

摘要

胆碱磷酸甘油(α-GPC)是一种在大脑中常见的胆碱基化合物和乙酰胆碱前体;它已被证明在治疗神经元损伤和增加乙酰胆碱(Ach)和脑源性神经营养因子(BDNF)水平方面非常有效,而这反过来又可以增强记忆力和认知功能。本研究旨在建立噪声和束缚双重应激的大鼠模型,以研究α-GPC 对双重应激后认知功能和神经元分化的影响。大鼠随机分为四组:对照组(CG)、α-GPC 对照组(CDG)、噪声-束缚应激组(NRSG)和噪声-束缚应激+α-GPC 组(NRSDG)。实验组每天同时暴露于 110 分贝声压级(SPL)白噪声和束缚 3 小时,共 7 天。应激暴露后第 7 天,给予α-GPC(400mg/kg)口服。NRSG 显示出记忆功能下降、应激激素增加、听力损失和大脑神经元损伤。在 NRSG 的海马体中,观察到 IL-1β表达显著增加,而胆碱乙酰转移酶(ChAT)和 BDNF 的表达均降低。相反,NRSDG 与 NRSG 相比表现出更好的记忆功能,这表明α-GPC 具有神经保护作用。此外,NRSDG 表现出免疫反应降低,ChAT 和 BDNF 表达增加以及海马体中的神经母细胞表达增加,这表明α-GPC 增强了 BDNF 的表达并保护了海马体中未成熟细胞的活性。据我们所知,这是第一项研究表明,α-GPC 通过促进应激动物模型中的神经元分化来保护认知功能障碍。

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