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维生素 D 可减轻脑室注射 STZ 诱导的散发性阿尔茨海默病的认知缺陷和神经炎症反应。

Vitamin D attenuates cognitive deficits and neuroinflammatory responses in ICV-STZ induced sporadic Alzheimer's disease.

机构信息

Pharmacology Research Laboratory, University Institute of Pharmaceutical Sciences (UIPS), UGC Centre of Advanced Study, Panjab University, Chandigarh, 160 014, India.

出版信息

Inflammopharmacology. 2018 Feb;26(1):39-55. doi: 10.1007/s10787-017-0372-x. Epub 2017 Jul 12.

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by intracellular neurofibrillary tangles and extracellular Aβ deposition. Growing experimental evidence indicate diverse biological effects of vitamin D including antioxidant, neuroprotective, anti-inflammatory and cardiovascular benefits. However, the underlying neuroprotective mechanism of vitamin D is still largely elusive. Therefore, the present study was aimed to investigate the neuroprotective effects of vitamin D on ICV-STZ induced sporadic AD. Our study demonstrated that vitamin D3 pretreatment significantly improved spatial learning and memory functions and effectively mitigated ICV-STZ mediated neuronal oxidative stress, mitochondrial aberrations and improved cholinergic functions. Moreover, vitamin D attenuated hippocampal neuroinflammatory response and reduced neuronal death in cortex and hippocampus. Our findings indicated that prophylactic vitamin D supplementation ameliorated ICV-STZ mediated neurobehavioral alterations, oxidative stress and neuroinflammation thereby improving cholinergic functions and reversed degenerative changes in brain. Thus, our study further provides evidence for its therapeutic supplementation for various neurodegenerative disorders including AD.

摘要

阿尔茨海默病(AD)是一种进行性神经退行性疾病,其特征是细胞内神经原纤维缠结和细胞外 Aβ 沉积。越来越多的实验证据表明维生素 D 具有多种生物学效应,包括抗氧化、神经保护、抗炎和心血管益处。然而,维生素 D 的潜在神经保护机制在很大程度上仍未被揭示。因此,本研究旨在探讨维生素 D 对脑室注射链脲佐菌素(ICV-STZ)诱导的散发性 AD 的神经保护作用。我们的研究表明,维生素 D3 预处理可显著改善空间学习和记忆功能,并有效减轻 ICV-STZ 介导的神经元氧化应激、线粒体异常和改善胆碱能功能。此外,维生素 D 可减轻海马神经炎症反应,减少皮质和海马中的神经元死亡。我们的研究结果表明,预防性维生素 D 补充可改善 ICV-STZ 介导的神经行为改变、氧化应激和神经炎症,从而改善胆碱能功能并逆转大脑的退行性变化。因此,本研究进一步为其在包括 AD 在内的各种神经退行性疾病中的治疗性补充提供了证据。

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