Abstract：
Synaptic abnormalities in synaptic proteins are the initial hallmarks of Alzheimer\'s disease (AD). The higher level of palmitoylation of synaptic proteins was closely associated with amyloid-β (Aβ) in AD. Cattle encephalon glycoside and ignotin (CEGI) have been shown to act as multitarget neurotrophic agents in APPswe/PS1dE9 (APP/PS1) transgenic AD mice. However, it is not clear whether CEGI can influence Aβ deposition or whether it does so by the regulation of protein palmitoylation and expression of synaptic proteins in transgenic AD mice.
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.
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.
摘要：
突触蛋白中的突触异常是阿尔茨海默病(AD)的最初标志。AD中突触蛋白的棕榈酰化水平较高与淀粉样β（Aβ）密切相关。牛脑苷和肌动蛋白（CEGI）已被证明在APPswe/PS1dE9（APP/PS1）转基因AD小鼠中可作为多靶标神经营养剂。然而,尚不清楚CEGI是否可以影响Aβ沉积，或者是否可以通过调节转基因AD小鼠的蛋白棕榈酰化和突触蛋白的表达来影响Aβ沉积。
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。
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。
