Liang Zhong-Qin, Wang Xiao-Xia, Wang Yumei, Chuang De-Maw, DiFiglia Marian, Chase Thomas N, Qin Zheng-Hong
Department of Pharmacology, Soochow University School of Medicine, Suzhou 215007, P.R. China.
Neurobiol Dis. 2005 Nov;20(2):562-73. doi: 10.1016/j.nbd.2005.04.011.
The present studies evaluated the potential contribution of Bcl-2, p53, and c-Myc to the differential vulnerability of striatal neurons to the excitotoxin quinolinic acid (QA). In normal rat striatum, Bcl-2 immunoreactivity (Bcl-2-i) was most intense in large aspiny interneurons including choline acetyltransferase positive (CAT+) and parvalbumin positive (PARV+) neurons, but low in a majority of medium-sized neurons. In human brain, intense Bcl-2-i was seen in large striatal neurons but not in medium-sized spiny projection neurons. QA produced degeneration of numerous medium-sized neurons, but not those enriched in Bcl-2-i. Many Bcl-2-i-enriched interneurons including those with CAT+ and PARV+ survived QA injection, while medium-sized neurons labeled for calbindin D-28K (CAL D-28+) did not. In addition, proapoptotic proteins p53-i and c-Myc-i were robustly induced in medium-sized neurons, but not in most large neurons. The selective vulnerability of striatal medium spiny neurons to degeneration in a rodent model of Huntington's disease appears to correlate with their low levels of Bcl-2-i and high levels of induced p53-i and c-Myc-i.
本研究评估了Bcl-2、p53和c-Myc对纹状体神经元对兴奋性毒素喹啉酸（QA）的不同易损性的潜在作用。在正常大鼠纹状体中，Bcl-2免疫反应性（Bcl-2-i）在包括胆碱乙酰转移酶阳性（CAT+）和小白蛋白阳性（PARV+）神经元在内的大型无棘中间神经元中最为强烈，但在大多数中型神经元中较低。在人脑的大型纹状体神经元中可见强烈的Bcl-2-i，但在中型棘状投射神经元中未见。QA导致大量中型神经元变性，但富含Bcl-2-i的神经元未变性。许多富含Bcl-2-i的中间神经元，包括那些CAT+和PARV+的中间神经元，在注射QA后存活下来，而标记为钙结合蛋白D-28K（CAL D-28+）的中型神经元则没有存活。此外，促凋亡蛋白p53-i和c-Myc-i在中型神经元中强烈诱导，但在大多数大型神经元中未诱导。在亨廷顿病啮齿动物模型中，纹状体中型棘状神经元对变性的选择性易损性似乎与其低水平的Bcl-2-i以及高水平的诱导型p53-i和c-Myc-i相关。
