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葡萄柚黄酮对阿尔茨海默病模型大鼠神经递质、突触传递及相关学习记忆作用的可能机制。

Possible mechanism of Vitis vinifera L. flavones on neurotransmitters, synaptic transmission and related learning and memory in Alzheimer model rats.

机构信息

College of Basic Medical, Xinjiang Medical University, No.393, Xinyi Road, Urumqi, 830011, Xinjiang, People's Republic of China.

College of Public Health, Xinjiang Medical University, Urumqi, 830054, People's Republic of China.

出版信息

Lipids Health Dis. 2018 Jul 4;17(1):152. doi: 10.1186/s12944-018-0708-6.

Abstract

BACKGROUND

This study explored the possible mechanism of flavones from Vitis vinifera L. (VTF) on neurotransmitters, synaptic transmission and related learning and memory in rats with Alzheimer disease (AD).

METHODS

The researchers injected amyloid-β into the hippocampus to establish AD model rats. The Sprague-Dawley (SD) rats were divided into a control group, a donepezil group, an AD model group, a VTF low-dose group, a VTF medium-dose group and a VTF high-dose group. The researchers detected the activity of choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) according to kit instructions. The protein expression of brain-derived neurotrophic factor (BDNF), synaptotagmin-1 (SYT1) and cyclic adenosine monophosphate response element binding protein (CREB) in the rats' hippocampi was detected by immunohistochemistry and Western blot, and the gene expression of cAMP-regulated enhancer (CRE) was detected by real-time quantitative polymerase chain reaction (PCR).

RESULTS

VTF may enhance the protein expression of p-CREB, BDNF and SYT1 in rat hippocampi, depending on dose. The messenger RNA (mRNA) level of CREB was significantly higher in the VTF high-dose group than in the model group, which was consistent with the results of Western blotting. VTF may reduce the activity of AChE and increase that of ChAT in rat hippocampi. Finally, VTF effectively improved the learning and memory abilities of AD rats.

CONCLUSIONS

VTF can promote synaptic plasticity and indirectly affect the expression of cholinergic neurotransmitters, which may be one mechanism of VTF protection in AD rats.

摘要

背景

本研究探讨了葡萄(Vitis vinifera L.)类黄酮对阿尔茨海默病(AD)大鼠神经递质、突触传递及相关学习记忆的可能作用机制。

方法

研究人员向大鼠海马内注射淀粉样β蛋白构建 AD 模型,将 Sprague-Dawley(SD)大鼠随机分为对照组、多奈哌齐组、AD 模型组、VTF 低剂量组、VTF 中剂量组和 VTF 高剂量组,根据试剂盒说明书检测大鼠海马组织中胆碱乙酰转移酶(ChAT)和乙酰胆碱酯酶(AChE)的活性,采用免疫组化和 Western blot 法检测大鼠海马脑源性神经营养因子(BDNF)、突触结合蛋白 1(SYT1)和环磷酸腺苷反应元件结合蛋白(CREB)的蛋白表达,实时荧光定量聚合酶链式反应(PCR)法检测 cAMP 反应元件(CRE)的基因表达。

结果

VTF 可增强 AD 大鼠海马内 p-CREB、BDNF 和 SYT1 的蛋白表达,且呈剂量依赖性,VTF 高剂量组 CREB 基因的信使 RNA(mRNA)水平显著高于模型组,与 Western blot 结果一致。VTF 可降低 AD 大鼠海马内 AChE 的活性,提高 ChAT 的活性。VTF 可有效改善 AD 大鼠的学习记忆能力。

结论

VTF 可促进突触可塑性,间接影响胆碱能神经递质的表达,这可能是 VTF 对 AD 大鼠发挥保护作用的机制之一。

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