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| 对淀粉样肽高度敏感的基底前脑胆碱能神经元的一个烟碱乙酰胆碱受体新亚型 |
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| A novel nicotinic acetylcholine receptor subtype in basal forebrain cholinergic neurons with high sensitivity to amyloid peptides |
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| Liu Q., Huang Y., Xue F., Simard A., DeChon J., Li G., Zhang J., Lucero L., Wang M., Sierks M., Hu G., Chang Y., Lukas R.J., Wu J. 2009/5/29 18:40:20 |
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Journal of Neuroscience, 2009, Volume 29, Issue 4
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| Nicotinic acetylcholine receptors (nAChRs) containing α7 subunits are thought to assemble as homomers. α7-nAChR function has been implicated in learning and memory, and alterations of α7-nAChR have been found in patients with Alzheimer's disease (AD). Here we report findings consistent with a novel, naturally occurring nAChR subtype in rodent, basal forebrain cholinergic neurons. In these cells, α7 subunits are coexpressed, colocalize, and coassemble with β2 subunit(s). Compared with homomeric α7-nAChRs from ventral tegmental area neurons, functional, presumably heteromeric α7β;2-nAChRs on cholinergic neurons freshly dissociated from medial septum/diagonal band (MS/DB) exhibit relatively slow kinetics of whole-cell current responses to nicotinic agonists and are more sensitive to the β;2 subunit-containing nAChR-selective antagonist, dihydro-β- erythroidine (DHβE). Interestingly, presumed, heteromeric α7β2-nAChRs are highly sensitive to functional inhibition by pathologically relevant concentrations of oligomeric, but not monomeric or fibrillar, forms of amyloid β1-42 (Aβ1-42). Slow whole-cell current kinetics, sensitivity to DHβE, and specific antagonism by oligomeric Aβ1-42 also are characteristics of heteromeric α7β2-nAChRs, but not of homomeric α7-nAChRs, heterologously expressed in Xenopus oocytes. Moreover, choline-induced currents have faster kinetics and less sensitivity to Aβ when elicited from MS/DB neurons derived from nAChR β2 subunit knock-out mice rather than from wild-type mice. The presence of novel, functional, heteromeric α7β2-nAChRs on basal forebrain cholinergic neurons and their high sensitivity to blockade by low concentrations of oligomeric Aβ1-42 suggests possible mechanisms for deficits in cholinergic signaling that could occur early in the etiopathogenesis of AD and might be targeted by disease therapies. Copyright © 2009 Society for Neuroscience. |
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| Correspondence Address: Wu, J.; Division of Neurology, Barrow Neurological Institute, 350 West Thomas Road, Phoenix, AZ 85013-4496, United States; email: jie.wu@chw.edu |
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 疾病资源中心
王燕燕 王曙
上海交通大学附属瑞金医院内分泌科
患者，女，69岁。2009年1月无明显诱因下出现乏力，当时程度较轻，未予以重视。2009年3月患者乏力症状加重，尿色逐渐加深，大便习惯改变，颜色变淡。4月18日入我院感染科治疗，诉轻度头晕、心慌，体重减轻10kg。无肝区疼痛，无发热，无腹痛、腹泻、腹胀、里急后重，无恶性、呕吐等。入院半月前于外院就诊，查肝功能：ALT 601IU/L，AST 785IU/L，TBIL 97.7umol/L，白蛋白 41g/L，甲状腺功能：游离T3 30.6pmol/L，游离T4 51.9pmol/L，心电图示快速房颤。
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