Dimebon对小鼠中型多棘神经元NMDA激活电流的影响
收稿日期: 2014-08-21
网络出版日期: 2015-02-12
Effect of dimebon on NMDA-activated current in mice medium spiny neuron
Received date: 2014-08-21
Online published: 2015-02-12
目的 探讨药物Dimebon在阿尔茨海默氏病（AD）和亨廷顿氏病（HD）的药理作用。方法 采用膜片钳技术在培养的小鼠纹状体中型多棘神经元（medium spiny striatal neurons，MSN）上观察不同浓度的Dimebon对NMDA (N-methyl-D-aspartic acid)受体激活电流的影响。结果 高浓度的Dimebon抑制NMDA激活电流，而低浓度的Dimebon增强NMDA 激活电流, 从而下调NMDA 受体。结论 Dimebon对NMDA受体激活电流的影响有双重作用，依Dimebon浓度的不同而不同，为临床用药提供依据。
关键词： ; Dimebon; 中型多棘神经元; NMDA受体激活电流
许晓利 , 李琴 , 宋露 , Ilya Bezprozvanny . Dimebon对小鼠中型多棘神经元NMDA激活电流的影响[J]. 中国临床解剖学杂志, 2015 , 33(1) : 89 -92 . DOI: 10.13418/j.issn.1001-165x.2015
Objective Dimebon is an antihistamine compound which has been proposed to treat neurodegenerative disorders, but the mechanism remain elusive. To explore Dimebon effection on Alzheimer's disease and Huntington's disease. Method Membrane currents were measured by using whole cell patch clamp techniques. the influence ofdifferent concentration of Dimebon on NMDA -activated currents in primary Medium Spiny Striatal Neuronal cultures (MSN) from wild type (WT) mice were studied. Results 1~50 μmol/L Dimebon inhibited NMDA activated currents, but 0.1~0.5μmol/L increased NMDA activated currents. Conclusion Dimebon has dual function on NMDA receptors.
Key words： Dimebon; ; Medium spiny striatal neurons; NMDA receptor
［1］Bachurin S, Bukatina E, Lermontova N, et al. Antihistamine agent Dimebon as a novel neuroprotector and a cognition enhancer［J］. Ann N Y Acad Sci, 2001,939:425-435.
［2］ Bezprozvanny I, Hayden MR. Deranged neuronal calcium signaling and Huntington disease［J］. Biochem Biophys Res Commun ,2004, 322(4):1310-1317.
［3］ Tang TS, Slow E, Lupu V, et al. Disturbed Ca2+ signaling and apoptosis of medium spiny neurons in Huntington's disease
[J].Proc Natl Acad Sci USA, 2005, 102(7):2602-2607.
［4］ Wu J, Li Q, Bezprozvanny I, et al. Evaluation of Dimebon in cellular model of Huntington's disease［J］.Mol Neurodegener, 2008，3:15.
［5］ Grigorev VV, Dranyi OA, Bachurin SO. Comparative study of action mechanisms of dimebon and memantine on AMPAand NMDA-subtypes glutamate receptors in rat cerebral neurons［J］. Bull Exp Biol Med ,2003, 136(5):474-477.
［6］ Lermontova NN, Redkozubov AE, Shevtsova EF,et al. Dimebon and tacrine inhibit neurotoxic action of beta-amyloid in culture and block L-type Ca(2+) channels［J］.Bull Exp Biol Med ,2001, 132(5):1079-1083.
［7］ Bachurin SO, Shevtsova EP, Kireeva EG, et al. Mitochondria as a target for neurotoxins and neuroprotective agents［J］. Ann N Y Acad Sci,2003, 993:334-344.
［8］ Doody RS, Gavrilova SI, Sano M, et al. Effect of dimebon on cognition,activities of daily living, behaviour, and global function in patients with mild-to-moderate Alzheimer's disease:a randomised, double-blind,placebo-controlled study
[J]. Lancet,2008,372(9634):207-215.
/
| 〈 |
|
〉 |
京ICP备08002354号-3
