Pang Zhi-Ping, Deng Ping, Ruan Yi-Wen, Xu Zao C
Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.
J Neurosci. 2002 Dec 15;22(24):10948-57. doi: 10.1523/JNEUROSCI.22-24-10948.2002.
Spiny neurons in the neostriatum die within 24 hr after transient global ischemia, whereas large aspiny (LA) neurons remain intact. To reveal the mechanisms of such selective cell death after ischemia, excitatory neurotransmission was studied in LA neurons before and after ischemia. The intrastriatally evoked fast EPSCs in LA neurons were depressed < or =24 hr after ischemia. The concentration-response curves generated by application of exogenous glutamate in these neurons were approximately the same before and after ischemia. A train of five stimuli (100 Hz) induced progressively smaller EPSCs, but the proportion of decrease in EPSC amplitude at 4 hr after ischemia was significantly smaller compared with control and at 24 hr after ischemia. Parallel depression of NMDA receptor and AMPA receptor-mediated EPSCs was also observed after ischemia, supporting the involvement of presynaptic mechanisms. The adenosine A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine blocked the inhibition of evoked EPSCs at 4 hr after ischemia but not at 24 hr after ischemia. Electron microscopic studies demonstrated that the most presynaptic terminals in the striatum had a normal appearance at 4 hr after ischemia but showed degenerating signs at 24 hr after ischemia. These results indicated that the excitatory neurotransmission in LA neurons was depressed after ischemia via presynaptic mechanisms. The depression of EPSCs shortly after ischemia might be attributable to the enhanced adenosine A1 receptor function on synaptic transmission, and the depression at late time points might result from the degeneration of presynaptic terminals.
新纹状体中的棘状神经元在短暂性全脑缺血后24小时内死亡，而大的无棘（LA）神经元则保持完整。为了揭示缺血后这种选择性细胞死亡的机制，对缺血前后LA神经元的兴奋性神经传递进行了研究。缺血后≤24小时，LA神经元纹状体内诱发的快速兴奋性突触后电流（fast EPSCs）受到抑制。在这些神经元中，应用外源性谷氨酸产生的浓度-反应曲线在缺血前后大致相同。一串五个刺激（100 Hz）诱发的EPSCs逐渐变小，但与对照组相比，缺血后4小时EPSC幅度的减小比例明显较小，且在缺血后24小时也是如此。缺血后还观察到NMDA受体和AMPA受体介导的EPSCs平行抑制，这支持了突触前机制的参与。腺苷A1受体拮抗剂8-环戊基-1,3-二丙基黄嘌呤在缺血后4小时阻断了诱发EPSCs的抑制，但在缺血后24小时则没有。电子显微镜研究表明，纹状体中大多数突触前终末在缺血后4小时外观正常，但在缺血后24小时出现退化迹象。这些结果表明，缺血后LA神经元的兴奋性神经传递通过突触前机制受到抑制。缺血后不久EPSCs的抑制可能归因于腺苷A1受体对突触传递功能的增强，而后期的抑制可能是由于突触前终末的退化所致。
