Time-dependent effect of oligomeric amyloid-β (1-42)-induced hippocampal neurodegeneration in rat model of Alzheimer's disease
Time-dependent effect of oligomeric amyloid-β (1-42)-induced hippocampal neurodegeneration in rat model of Alzheimer's disease
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DOI：
10.1080/01616412.2018.1544745
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发表时间：
2019-01-01
影响因子：
1.9
通讯作者：
Anusuyadevi, Muthuswamy
中科院分区：
文献类型：
--
作者：
Karthick, Chennakesavan;Nithiyanandan, Saravanan;Anusuyadevi, Muthuswamy
目的：阿尔茨海默病（Alzheimer's disease，AD）是以不溶性淀粉样蛋白β（amyloid-beta，A β）肽斑块异常沉积、缠结形成和突触功能障碍为特征的疾病。这些导致神经元回路功能受损，并由于神经递质受体的激活而改变行为反应。最近，它已被牵连，A β影响N-甲基o-天冬氨酸（NMDA）受体激活AD，但其分子机制仍不清楚。因此，研究寡聚体A β（（1-42））（oA β（1 - 42））对AD大鼠模型中编码NMDA和乙酰胆碱受体的基因mRNA表达的时程效应就成为一个具体的目的。方法：采用立体定向手术将合成的A β肽聚集体注射到大鼠脑内海马区。实验结束时采用八臂桡臂迷宫任务进行行为学分析。结果：oA β（1-42）可降低α 7-烟碱型乙酰胆碱受体基因表达水平，增加NMDA受体2A、2B亚单位mRNA表达水平。特别是，oA β（1-42）聚集体增加了保留时间，并改变了大鼠注射15天后的行为反应。结论：oA β（1- 42）急性暴露可调节成年大鼠海马神经递质受体和胆碱能受体基因的差异表达，并呈时间依赖性，反映了海马神经回路系统的变化，是学习记忆障碍的基础。
Objective: Alzheimer's disease (AD) is characterized with an abnormal deposition of insoluble amyloid-beta (A beta) peptide plaques, tangles formation and synaptic dysfunction. These result in impaired functioning of neuronal circuits and alter the behavioral response owing to activation of neurotransmitter receptors. Recently, it has been implicated that A beta influences N-methyl o-aspartate (NMDA) receptor activation in AD; however, the molecular mechanism underlying remains unclear. Thus, emerged specific aim to study the time-course effect of oligomeric A beta((1-42)) (oA beta(1-42)) on the mRNA expression of genes encoding NMDA and acetylcholine receptors in the rat model of AD.Methods: Aggregated forms of synthetic A beta peptides were injected bilaterally into the intrahippocampal region of rat brain using stereotaxic surgery. Behavioral analysis was performed using eight-arm Radial Arm Maze task at the end of experimental period. Euthanized rat brain hippocampal tissue was used to study the mRNA expression of glutamatergic and cholinergic receptor using semiquantitative reverse transcription-polymerase chain reaction.Results: oA beta(1-42) decreased the gene expression level of alpha 7-nicotinic acetylcholine receptor and increased the mRNA expression of NMDA receptor 2A, and -2B subunits. In particular, oA beta(1-42) aggregates increased the retention time and altered the behavioral response in rats after 15 days of injection. Further, amyloid-beta(1-42) are highly expressed in 15 days after postinjection in hippocampus of adult rats.Conclusion: Acute exposure of oA beta(1-42) modulated differential gene expression of glutamatergic and cholinergic receptors in hippocampus of adult rats and is duration dependent reflecting changes in hippocampal circuitry system underlying learning and memory impairments.