积雪草改善老年Tg2576和野生型小鼠的认知功能,改变海马代谢组。

IF 2.8 Q2 NEUROSCIENCES
Journal of Alzheimer's disease reports Pub Date : 2024-12-04 eCollection Date: 2024-01-01 DOI:10.1177/25424823241296740
Donald G Matthews, Mona Khorani, Gerd Bobe, Maya Caruso, Armando Alcazar Magana, Nora E Gray, Joseph F Quinn, Jan F Stevens, Claudia S Maier, Amala Soumyanath
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引用次数: 0

摘要

背景:阿尔茨海默病(AD)是老龄化人口中日益严重的公共卫生问题,治疗方案有限。我们之前报道了积雪草草本水提取物(CAW)减轻AD和衰老小鼠模型的认知能力下降。目的:探讨老年Tg2576和野生型(WT)小鼠海马代谢组变化与CAW对认知功能和淀粉样蛋白-β (Aβ)斑块负荷的调节关系。方法:我们比较了20月龄Tg2576雌性小鼠及其WT窝仔在接受CAW(0、200或1000 mg/kg/d p.o)治疗3-5周后的认知功能、海马Aβ斑块负担和海马代谢物谱。认知测试包括情境恐惧反应(CFR)和新目标识别任务(NORT)。免疫组化法测定Aβ斑块负荷。采用液相色谱联用高分辨率串联质谱法获得小鼠海马代谢组学图谱。结果:CAW处理使Tg2576和WT小鼠的CFR和NORT表现呈剂量相关性改善。然而,虽然CFR与神经信号传导和糖基化神经酰胺水平相关,但NORT表现与溶血磷脂酰胆碱和氧化代谢物相关,而Aβ积累与兴奋性升高和抑制性神经传递抑制有关。在Tg2576小鼠中,CAW诱导的代谢物变化中只有一小部分代表了Tg2576与WT小鼠代谢物差异的逆转,这表明CAW的认知作用涉及其他途径。结论:CAW的认知作用机制超出了逆转Aβ积累的代谢作用。这些数据支持CAW在有或没有AD的老年人中管理记忆挑战的潜在应用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Centella asiatica improves cognitive function and alters the hippocampal metabolome of aged Tg2576 and wild-type mice.

Background: Alzheimer's disease (AD) is a growing public health problem in the aging population, with limited treatment options. We previously reported that Centella asiatica herb water extract (CAW) attenuates cognitive decline in murine models of AD and aging.

Objective: To explore changes in the hippocampal metabolome associated with CAW's modulation of cognitive function and amyloid-β (Aβ) plaque load in aged Tg2576 and wild-type (WT) mice.

Methods: We compared cognitive function, hippocampal Aβ plaque burden, and hippocampal metabolite profile in 20-month-old Tg2576 female mice and their WT littermates following 3-5 weeks treatment with CAW (0, 200, or 1000 mg/kg/d p.o.). Cognitive testing included contextual fear response (CFR) and novel object recognition task (NORT). Aβ plaque burden was measured via immunohistochemistry. Metabolomic profiles of mouse hippocampi were obtained using liquid chromatography coupled with high resolution tandem mass spectrometry.

Results: CAW treatment resulted in dose-related improvements in CFR and NORT performance of Tg2576 and WT mice. However, while CFR correlated with neurosignaling and glycosylated ceramide levels, NORT performance correlated with lysophosphatidylcholines and oxidized metabolites, and Aβ accumulation was linked to elevated excitatory and suppressed inhibitory neurotransmission. Only a subset of the metabolite changes induced by CAW in Tg2576 mice represented a reversal of metabolite differences between Tg2576 and WT mice, suggesting the involvement of other pathways in CAW's cognitive effects.

Conclusions: Mechanisms underlying CAW's cognitive effects extend beyond reversing metabolic effects of Aβ accumulation. The data support the potential use of CAW to manage memory challenges in aged individuals with or without AD.

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