Davis School of Gerontology, University of Southern California, Los Angeles, CA 90089-0191, USA.
Neuroscience. 2012 Jul 26;215:149-59. doi: 10.1016/j.neuroscience.2012.04.060. Epub 2012 Apr 30.
The striatum is particularly vulnerable to mitochondrial dysfunction and this problem is linked to pathology created by environmental neurotoxins, stimulants like amphetamine, and metabolic disease and ischemia. We studied the course of recovery following a single systemic injection of the mitochondrial complex II inhibitor 3-nitropropionic acid (3-NP) and found 3-NP caused lasting changes in motor behavior that were associated with altered activity-dependent plasticity at corticostriatal synapses in Fischer 344 rats. The changes in synapse behavior varied with the time after exposure to the 3-NP injection. The earliest time point studied, 24h after 3-NP, revealed 3-NP-induced an exaggeration of D1 Dopamine (DA) receptor dependent long-term potentiation (LTP) that reversed to normal by 48 h post-3-NP exposure. Thereafter, the likelihood and degree of inducing D2 DA receptor dependent long-term depression (LTD) gradually increased, relative to saline controls, peaking at 1 month after the 3-NP exposure. NMDA receptor binding did not change over the same post 3-NP time points. These data indicate even brief exposure to 3-NP can have lasting behavioral effects mediated by changes in the way DA and glutamate synapses interact.
纹状体特别容易受到线粒体功能障碍的影响，而这个问题与环境神经毒素、安非他命等兴奋剂以及代谢疾病和缺血引起的病理学有关。我们研究了单次系统性注射线粒体复合物 II 抑制剂 3-硝基丙酸（3-NP）后的恢复过程，发现 3-NP 导致运动行为的持久变化，这与费希尔 344 大鼠皮质纹状体突触的活性依赖性可塑性改变有关。突触行为的变化随著暴露于 3-NP 注射后的时间而变化。在研究的最早时间点，即 3-NP 注射后 24 小时，显示 3-NP 诱导 D1 多巴胺（DA）受体依赖性长时程增强（LTP）的夸大，在 3-NP 暴露后 48 小时恢复正常。此后，与生理盐水对照相比，D2 DA 受体依赖性长时程抑制（LTD）的诱导可能性和程度逐渐增加，在 3-NP 暴露后 1 个月达到峰值。在相同的 3-NP 后时间点，NMDA 受体结合没有变化。这些数据表明，即使短暂暴露于 3-NP 也会导致行为的持久影响，这是由 DA 和谷氨酸突触相互作用方式的改变介导的。
