Kumar Ujendra
Fraser Laboratories, Department of Medicine, Room M3-15, Royal Victoria Hospital, McGill University, 687 Pine Avenue West, Montreal, Que., Canada H3A 1A1.
Neurosci Res. 2004 May;49(1):29-38. doi: 10.1016/j.neures.2004.01.011.
The degeneration of selective and specific types of neurons is a characteristic feature in several neurodegenerative disorders. N-methyl-D-aspartate receptor (NMDAR) agonist quinolinic acid (QUIN)-induced excitotoxicity has been implicated in neurodegeneration and mimics Huntington's disease (HD) by the loss of medium-sized spiny projection neurons while sparing medium-sized aspiny interneurons in the striatum. Previous work suggests that somatostatin/neuropeptide Y (SST/NPY)-containing neurons are selectively preserved in HD due to the presence of nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) and the lack of NMDAR. In the present study, the distribution of somatostatin (SST), neuropeptide Y (NPY), nitric oxide synthase (nNOS), NMDA receptor type-1 (NR1), and the enzyme NADPH-d was determined in cultured striatal neurons with the effect of QUIN and N-methyl-D-aspartate (NMDA). SST/NPY-positive neurons, which constitute approximately 8-10% of striatal neurons, are selectively spared in QUIN/NMDA-treated cultures. nNOS and NADPH-d-positive neurons, comprising 3.8% of the neuronal population, also exhibit selective resistance to excitotoxicity. Most NR1-positive neurons, which constitute >80% of the total neuronal population, are lost in majority upon treatment with QUIN and NMDA. SST and NADPH-d-positive neurons also colocalize with Cu/Zn superoxide dismutase (Cu/Zn SOD). In conclusion, our results thus demonstrate that SST/NPY/nNOS-positive neurons are selectively spared in NMDA agonist-induced excitotoxicity, which could be attributed to the presence of Cu/Zn SOD and NADPH-d in addition to the low abundance of NMDAR on these neurons.
选择性和特定类型神经元的退化是几种神经退行性疾病的特征性表现。N-甲基-D-天冬氨酸受体（NMDAR）激动剂喹啉酸（QUIN）诱导的兴奋性毒性与神经退行性变有关，并且通过中型棘状投射神经元的丧失模拟亨廷顿病（HD），而纹状体中的中型无棘中间神经元则得以保留。先前的研究表明，由于存在烟酰胺腺嘌呤二核苷酸磷酸黄递酶（NADPH-d）且缺乏NMDAR，含生长抑素/神经肽Y（SST/NPY）的神经元在HD中被选择性保留。在本研究中，测定了培养的纹状体神经元中生长抑素（SST）、神经肽Y（NPY）、一氧化氮合酶（nNOS）、NMDAR1型受体（NR1）以及NADPH-d酶的分布，并观察了QUIN和N-甲基-D-天冬氨酸（NMDA）的作用。构成纹状体神经元约8%-10%的SST/NPY阳性神经元在QUIN/NMDA处理的培养物中被选择性保留。占神经元总数3.8%的nNOS和NADPH-d阳性神经元也表现出对兴奋性毒性的选择性抗性。构成神经元总数80%以上的大多数NR1阳性神经元在QUIN和NMDA处理后大部分丧失。SST和NADPH-d阳性神经元也与铜/锌超氧化物歧化酶（Cu/Zn SOD）共定位。总之，我们的结果表明，SST/NPY/nNOS阳性神经元在NMDA激动剂诱导的兴奋性毒性中被选择性保留，这可能归因于这些神经元上除了低丰度的NMDAR外，还存在Cu/Zn SOD和NADPH-d。
