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阿尔茨海默病淀粉样 β(1-42)诱导大鼠模型中颞叶皮层认知因素的日周期变化。

Daily oscillation of cognitive factors is modified in the temporal cortex of an amyloid β(1-42)-induced rat model of Alzheimer's disease.

机构信息

Laboratorio de Cronobiología, Facultad de Química, Bioquímica y Farmacia, Universidad Nacional de San Luis Instituto Multidisciplinario de Investigaciones Biológicas de San Luis (IMIBIO-SL), CONICET, Ejército de Los Andes 950, CP D5700HHW, San Luis, Argentina.

Laboratorio de Biología de la Reproducción (LABIR), Facultad de Química, Bioquímica y Farmacia, Universidad Nacional de San Luis, Instituto Multidisciplinario de Investigaciones Biológicas de San Luis (IMIBIO-SL), CONICET, Ejército de Los Andes 950, CP D5700HHW, San Luis, Argentina.

出版信息

Brain Res Bull. 2021 May;170:106-114. doi: 10.1016/j.brainresbull.2021.01.014. Epub 2021 Jan 27.

Abstract

Alzheimer's disease (AD) is a devastating disease characterized by loss of synapses and neurons in the elderly. Accumulation of the β-amyloid peptide (Aβ) in the brain is thought to be central to the pathogenesis of AD. ApoE plays a key role in normal and physiological clearance of Aß, since it facilitates the peptide intra- and extracellular proteolytic degradation. Besides the cognitive deficit, AD patients also show alterations in their circadian rhythms. The objective of this study was to investigate the effects of an i.c.v. injection of Aβ (1-42) peptide on the 24 h rhythms of Apo E, BMAL1, RORα, Bdnf and trkB mRNA and Aβ levels in the rat temporal cortex. We found that an i.c.v. injection of Aβ aggregates phase shifts daily Bdnf expression as well as Apo E, BMAL1, RORα, Aβ and decreased the mesor of TrkB rhythms. Thus, elevated Aβ peptide levels might modify the temporal patterns of cognition-related factors, probably; by affecting the clock factors rhythms as well as in the 24 h rhythms of Apo E.

摘要

阿尔茨海默病(AD)是一种破坏性疾病,其特征是老年人突触和神经元的丧失。大脑中β-淀粉样肽(Aβ)的积累被认为是 AD 发病机制的核心。载脂蛋白 E 在 Aß 的正常和生理清除中起着关键作用,因为它促进肽的细胞内和细胞外蛋白水解降解。除了认知缺陷外,AD 患者的昼夜节律也会发生改变。本研究的目的是研究脑室内注射 Aβ(1-42)肽对大鼠颞皮质中 Apo E、BMAL1、RORα、Bdnf 和 trkB mRNA 和 Aβ水平的 24 小时节律的影响。我们发现,脑室内注射 Aβ 聚集物会使 Bdnf 表达以及 Apo E、BMAL1、RORα、Aβ的日相位发生变化,并降低 TrkB 节律的中值。因此,升高的 Aβ 肽水平可能会改变与认知相关的因素的时间模式,可能是通过影响生物钟因素的节律以及 Apo E 的 24 小时节律。

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