In this study, we investigated the roles of CEGI in modulating postsynaptic density protein 95 (PSD-95) palmitoylation, Aβ pathologies, and expression of synaptic-associated proteins in APP/PS1 mice.
Five-month-old APP/PS1 mice were treated intraperitoneally with 6.6 mL/kg of CEGI for 6 weeks. At the end of the treatment period, APP/PS1 mice were subjected to Morris water maze to test their cognitive functions. Acyl-biotinyl exchange (ABE) for PSD-95 palmitoylation, immunofluorescent staining for expression of PSD-95, N-methyl-D-aspartic acid receptor subunit 2B (NR2B), and synaptotagmin 1 (SYT1) were assessed in mouse brain sections.
CEGI treatment in APP/PS1 mice significantly reduced Aβ deposition, relieved memory deficits, and decreased PSD-95 palmitoylation while markedly increasing the expression of PSD-95, NR2B, and SYT1 in the frontal cortex. There was a significant correlation between Aβ expression and PSD-95 palmitoylation in APP/PS1 mice.
Our findings demonstrate that CEGI improved AD-like neuropathology, possibly by inhibiting PSD-95 palmitoylation, improving learning memory, and enhancing expression of synaptic-associated proteins, representing a potential therapy for AD treatment.
在这项研究中,我们研究了CEGI在调节突触后密度蛋白95(PSD-95)棕榈酰化中的作用,Aβ病理学,和突触相关蛋白在APP/PS1小鼠中的表达。
5个月大的APP/PS1小鼠用6.6mL/kg的CEGI腹膜内处理6周。在治疗期结束时,使APP/PS1小鼠经受Morris水迷宫以测试其认知功能。用于PSD-95棕榈酰化的酰基-生物素交换(ABE),对PSD-95,N-甲基-D-天冬氨酸受体2B亚基(NR2B)表达的免疫荧光染色,在小鼠脑切片中评估突触蛋白1(SYT1)。
APP/PS1小鼠的CEGI治疗显著减少了Aβ沉积,缓解记忆缺陷,并降低PSD-95棕榈酰化,同时显着增加PSD-95,NR2B的表达,和SYT1在额叶皮层。APP/PS1小鼠中Aβ的表达与PSD-95棕榈酰化之间存在显着相关性。
我们的研究结果表明,CEGI改善了AD样神经病理学,可能通过抑制PSD-95棕榈酰化,改善学习记忆,增强突触相关蛋白的表达,代表AD治疗的潜在疗法。