Cepeda Carlos, Cummings Damian M, Hickey Miriam A, Kleiman-Weiner Max, Chen Jane Y, Watson Joseph B, Levine Michael S
Intellectual and Developmental Disabilities Research Center, David Geffen School of Medicine, University of California, Los Angeles, CA, USA and Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
PLoS Curr. 2010 Sep 20;2:RRN1182. doi: 10.1371/currents.RRN1182.
In the R6/2 mouse model of Huntington's disease (HD) we examined the effects of a number of behavioral and pharmacological manipulations aimed at rescuing the progressive loss of synaptic communication between cerebral cortex and striatum. Two cohorts of transgenic mice with ~110 and 210 CAG repeats were utilized. Exercise prevented the reduction in striatal medium-sized spiny neuron membrane capacitance but did not reestablish synaptic communication. Activation of adenosine A2A type receptors renormalized postsynaptic activity to some extent. Finally, the ampakine Cx614, which has been shown to prevent α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) receptor desensitization, slow deactivation, and facilitate glutamate release, induced significant increases in synaptic activity, albeit the effect was somewhat reduced in fully symptomatic, compared to control mice. With some limitations, each of these strategies can be used to delay and partially rescue phenotypic progression of HD in this model.
在亨廷顿舞蹈症（HD）的R6/2小鼠模型中，我们研究了一系列行为和药理学操作的效果，这些操作旨在挽救大脑皮层与纹状体之间突触通讯的渐进性丧失。我们使用了两组分别具有约110个和210个CAG重复序列的转基因小鼠。运动可防止纹状体中型棘状神经元膜电容降低，但无法重建突触通讯。腺苷A2A受体的激活在一定程度上使突触后活动恢复正常。最后，安帕金Cx614已被证明可防止α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）受体脱敏、减缓失活并促进谷氨酸释放，它可诱导突触活动显著增加，尽管与对照小鼠相比，在完全出现症状的小鼠中这种效果有所降低。尽管存在一些局限性，但这些策略中的每一种都可用于延缓并部分挽救该模型中HD的表型进展。
