α7 nicotinic receptor up-regulation in cholinergic basal forebrain neurons in Alzheimer disease
α7 nicotinic receptor up-regulation in cholinergic basal forebrain neurons in Alzheimer disease
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DOI：
10.1001/archneur.64.12.1771
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发表时间：
2007-12-01
影响因子：
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通讯作者：
Mufson, Elliott J.
中科院分区：
文献类型：
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作者：
Counts, Scott E.;He, Bin;Mufson, Elliott J.
背景：基底核（NB）基底皮质胆碱能投射神经元功能障碍与阿尔茨海默病（AD）的认知缺陷相关。基底核神经元接受胆碱能输入，表达烟碱乙酰胆碱受体（nAChRs）和毒碱乙酰胆碱受体（mAChRs），可能调节AD患者NB神经元的活性。尽管这些achr的改变发生在AD皮层，但在疾病进展过程中，nAChR和mAChR基因表达的缺陷是否发生在胆碱能NB神经元中，还没有详细的信息。目的：探讨胆碱能NB神经元中nAChR和mAChR基因表达在阿尔茨海默病进展过程中的变化。设计：通过定制设计的微阵列，通过单细胞AChR表达谱分析死前诊断为无认知障碍（NCI）、轻度认知障碍（MCI）或轻度至中度AD的受试者的单个NB神经元。设置：学术研究。参与者：参与者是拉什宗教秩序研究队列的成员。主要观察指标：实时定量聚合酶链反应验证微阵列结果。结果：与NCI和MCI患者相比，轻至中度AD患者胆碱能NB神经元α 7 nAChR信使RNA表达上调具有统计学意义(P
Background: Dysfunction of basocortical cholinergic projection neurons of the nucleus basalis (NB) correlates with cognitive deficits in Alzheimer disease (AD). Nucleus basalis neurons receive cholinergic inputs and express nicotinic acetylcholine receptors (nAChRs) and muscarinic AChRs (mAChRs), which may regulate NB neuron activity in AD. Although alterations in these AChRs occur in the AD cortex, there is little information detailing whether defects in nAChR and mAChR gene expression occur in cholinergic NB neurons during disease progression.Objective: To determine whether nAChR and mAChR gene expression is altered in cholinergic NB neurons during the progression of AD.Design: Individual NB neurons from subjects diagnosed ante mortem as having no cognitive impairment (NCI), mild cognitive impairment (MCI), or mild to moderate AD were analyzed by single-cell AChR expression profiling via custom-designed microarrays.Setting: Academic research.Participants: Participants were members of the Rush Religious Orders Study cohort.Main Outcome Measures: Real-time quantitative polymerase chain reaction was performed to validate micro-array findings.Results: Cholinergic NB neurons displayed a statistically significant up-regulation of alpha 7 nAChR messenger RNA expression in subjects with mild to moderate AD compared with those with NCI and MCI (P