Etomidate ameliorates Alzheimer-like neuropathology and cognitive impairment in APP/PS1 mice.

IF 2 4区 医学 Q3 PHYSIOLOGY
Journal of Physiology and Pharmacology Pub Date : 2025-02-01 Epub Date: 2025-03-18 DOI:10.26402/jpp.2025.1.04
H Liu, J Zhou, W W Yang
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引用次数: 0

Abstract

To investigate the effect and mechanism of etomidate on attenuating Alzheimer-like neuropathology and cognitive impairment in mice with Alzheimer's disease (AD). AD was modeled in vivo using amyloid precursor protein/presenilin 1 (APP/PS1) mice. After etomidate treatment, behavioral experiments and histopathological observation of hippocampus were performed. Hippocampal Aβ deposition was detected using immunofluorescence. AD was modeled in vitro using a HT22 cells which are an immortalized cell line derived from primary mouse hippocampal neurons induced by Aβ1-42. Cell viability, apoptosis rate and LDH release were detected after etomidate intervention. Synaptic proteins were detected by mmunofluorescence or Western blot, and neurotransmitters and inflammatory factors were detected by ELISA. Etomidate improved the memory ability, novel object cognition ability, and spatial learning of APP/PS1 mice. The improvement of cognitive function and memory ability may be due to the recovery effect of etomidate on hippocampal pathological changes in APP/PS1 mice, including reducing Aβ deposition, neuron and synaptic loss. Etomidate also regulated neuroinflammation and the release of neurotransmitters GABA and 5-HT in APP/PS1 mice. Etomidate effectively reversed Aβ1-42-induced hippocampal neuronal damage, which was reflected in the improvement of cell viability and the inhibition of cytotoxicity, apoptosis and pro-inflammatory factors. Etomidate reversed the inhibition of the expression of synaptophysin (SYP) and postsynaptic density protein-95 (PSD-95) induced by Aβ1-42 in vitro. After etomidate intervention, the expression of serotonin 1A receptor (5HT1A) and gamma-aminobutyric acid type A receptor subunit alpha1 (GABRA1) in Aβ1-42-injured HT22 cells were up-regulated, and free calcium ion was increased. In conclusion, etomidate ameliorates Alzheimer-like neuropathology and cognitive impairment in APP/PS1 mice, indicating that etomidate may be a potentially useful drug for the treatment of AD.

依托咪酯改善APP/PS1小鼠阿尔茨海默样神经病理和认知障碍
探讨依托咪酯减轻阿尔茨海默病(AD)小鼠阿尔茨海默样神经病理和认知功能障碍的作用及其机制。采用淀粉样蛋白前体蛋白/早老素1 (APP/PS1)小鼠在体内建立AD模型。经依托咪酯治疗后,进行行为学实验和海马组织病理学观察。免疫荧光法检测海马Aβ沉积。采用a - β1-42诱导的小鼠海马原代神经元HT22细胞建立AD体外模型。用依托咪酯干预后检测细胞活力、凋亡率和LDH释放量。免疫荧光或Western blot检测突触蛋白,ELISA检测神经递质和炎症因子。依托咪酯可提高APP/PS1小鼠的记忆能力、新物体认知能力和空间学习能力。认知功能和记忆能力的改善可能是由于依托咪酯对APP/PS1小鼠海马病理改变的恢复作用,包括减少Aβ沉积、神经元和突触的丧失。依托咪酯还能调节APP/PS1小鼠的神经炎症和神经递质GABA和5-HT的释放。依托咪酯可有效逆转a β1-42诱导的海马神经元损伤,表现为提高细胞活力,抑制细胞毒性、凋亡和促炎因子。依托咪酯可逆转Aβ1-42诱导的突触体素(SYP)和突触后密度蛋白-95 (PSD-95)表达抑制。依托咪酯干预后,Aβ1-42损伤HT22细胞中5 -羟色胺1A受体(5HT1A)和γ -氨基丁酸A型受体亚基α 1 (GABRA1)表达上调,游离钙离子增加。综上所述,依托咪酯可改善APP/PS1小鼠的阿尔茨海默样神经病理和认知功能障碍,表明依托咪酯可能是治疗AD的潜在有效药物。
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来源期刊
CiteScore
4.00
自引率
22.70%
发文量
0
审稿时长
6-12 weeks
期刊介绍: Journal of Physiology and Pharmacology publishes papers which fall within the range of basic and applied physiology, pathophysiology and pharmacology. The papers should illustrate new physiological or pharmacological mechanisms at the level of the cell membrane, single cells, tissues or organs. Clinical studies, that are of fundamental importance and have a direct bearing on the pathophysiology will also be considered. Letters related to articles published in The Journal with topics of general professional interest are welcome.
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