Disturbed neurotransmitter transporter expression in Alzheimer's disease brain.
Disturbed neurotransmitter transporter expression in Alzheimer's disease brain.
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DOI：
10.3233/jad-2011-110002
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发表时间：
2011
期刊：
影响因子：
--
通讯作者：
Rao JS
中科院分区：
文献类型：
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作者：
Chen KH;Reese EA;Kim HW;Rapoport SI;Rao JS
阿尔茨海默病（AD）是一种神经退行性疾病，其特征是记忆丧失以及痴呆的行为和心理症状。不同神经递质（谷氨酸、乙酰胆碱、多巴胺和血清素）的不平衡已被认为是 AD 行为症状的神经生物学基础。与 AD 神经传递失衡相关的分子变化尚不清楚。我们假设囊泡谷氨酸转运蛋白（VGLUT）、兴奋性氨基酸转运蛋白（EAAT）、囊泡乙酰胆碱转运蛋白（VAChT）、血清素再摄取转运蛋白（SERT）或多巴胺再摄取转运蛋白（DAT）对神经递质的再摄取改变与AD的神经传递失衡有关。我们通过检查 10 名 AD 患者和 10 名匹配的非 AD 对照者死后前额皮质中这些转运蛋白的蛋白质和 mRNA 水平来检验这一假设。与对照组相比，AD 中 VGLUT、EAAT1-3、VAChT 和 SERT 的蛋白质和 mRNA 水平显着降低。 DAT 和儿茶酚 O-甲基转移酶 (COMT) 的表达没有变化。 VGLUT 和 EAAT 的减少可能会导致谷氨酸循环的改变，而 SERT 的减少可能会加剧 AD 的抑郁症状。 VAChT 表达的减少可能导致 AD 中公认的胆碱能缺陷。改变的神经递质转运蛋白可能有助于 AD 的病理生理学，并且是潜在的治疗目标。
Alzheimer disease (AD) is a neurodegenerative disorder characterized by memory loss and behavioral and psychological symptoms of dementia. An imbalance of different neurotransmitters – glutamate, acetylcholine, dopamine, and serotonin - has been proposed as the neurobiological basis of behavioral symptoms in AD. The molecular changes associated with neurotransmission imbalance in AD are not clear. We hypothesized that altered reuptake of neurotransmitters by vesicular glutamate transporters (VGLUTs), excitatory amino acid transporters (EAATs), the vesicular acetylcholine transporter (VAChT), the serotonin reuptake transporter (SERT), or the dopamine reuptake transporter (DAT)) are involved in the neurotransmission imbalance in AD. We tested this hypothesis by examining protein and mRNA levels of these transporters in postmortem prefrontal cortex from 10 AD patients and 10 matched non-AD controls. Compared with controls, protein and mRNA levels of VGLUTs, EAAT1–3, VAChT, and SERT were reduced significantly in AD. Expression of DAT and catechol O-methyltransferase (COMT) was unchanged. Reduced VGLUTs and EAATs may contribute to an alteration in glutamatergic recycling, and reduced SERT could exacerbate depressive symptoms in AD. The reduced VAChT expression could contribute to the recognized cholinergic deficit in AD. Altered neurotransmitter transporters could contribute to the pathophysiology of AD and are potential targets for therapy.