Fourie C, Kim E, Waldvogel H, Wong J M, McGregor A, Faull R L M, Montgomery J M
Department of Physiology, Centre for Brain Research, University of Auckland, Private Bag 92019, Auckland, New Zealand.
Department of Anatomy with Radiology, Centre for Brain Research, University of Auckland, Private Bag 92019, Auckland, New Zealand.
J Neurodegener Dis. 2014;2014:938530. doi: 10.1155/2014/938530. Epub 2014 Jan 16.
NMDA and AMPA-type glutamate receptors and their bound membrane-associated guanylate kinases (MAGUKs) are critical for synapse development and plasticity. We hypothesised that these proteins may play a role in the changes in synapse function that occur in Huntington's disease (HD) and Parkinson's disease (PD). We performed immunohistochemical analysis of human postmortem brain tissue to examine changes in the expression of SAP97, PSD-95, GluA2 and GluN1 in human control, and HD- and PD-affected hippocampus and striatum. Significant increases in SAP97 and PSD-95 were observed in the HD and PD hippocampus, and PSD95 was downregulated in HD striatum. We observed a significant increase in GluN1 in the HD hippocampus and a decrease in GluA2 in HD and PD striatum. Parallel immunohistochemistry experiments in the YAC128 mouse model of HD showed no change in the expression levels of these synaptic proteins. Our human data show that major but different changes occur in glutamatergic proteins in HD versus PD human brains. Moreover, the changes in human HD brains differ from those occurring in the YAC128 HD mouse model, suggesting that unique changes occur at a subcellular level in the HD human hippocampus.
N-甲基-D-天冬氨酸（NMDA）和α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）型谷氨酸受体及其结合的膜相关鸟苷酸激酶（MAGUKs）对突触发育和可塑性至关重要。我们推测这些蛋白质可能在亨廷顿舞蹈病（HD）和帕金森病（PD）中发生的突触功能变化中发挥作用。我们对人类死后脑组织进行了免疫组织化学分析，以检查人类对照组、HD和PD患者受影响的海马体和纹状体中突触相关蛋白97（SAP97）、突触后密度蛋白95（PSD-95）、谷氨酸受体2（GluA2）和N-甲基-D-天冬氨酸受体1（GluN1）表达的变化。在HD和PD患者的海马体中观察到SAP97和PSD-95显著增加，而在HD患者的纹状体中PSD95表达下调。我们观察到HD患者海马体中GluN1显著增加，而在HD和PD患者的纹状体中GluA2减少。在HD的YAC128小鼠模型中进行的平行免疫组织化学实验显示这些突触蛋白的表达水平没有变化。我们的人体数据表明，HD与PD患者大脑中的谷氨酸能蛋白发生了重大但不同的变化。此外，HD患者大脑中的变化与YAC128 HD小鼠模型中的变化不同，这表明HD患者海马体在亚细胞水平上发生了独特的变化。
