Unique responses to mitochondrial complex I inhibition in tuberoinfundibular dopamine neurons may impart resistance to toxic insult
Unique responses to mitochondrial complex I inhibition in tuberoinfundibular dopamine neurons may impart resistance to toxic insult
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DOI：
10.1016/j.neuroscience.2007.05.007
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发表时间：
2007-07-13
期刊：
影响因子：
3.3
通讯作者：
Goudreau, J. L.
中科院分区：
文献类型：
--
作者：
Behrouz, B.;Drolet, R. E.;Goudreau, J. L.
帕金森氏病（PD）是一种引起中脑黑质纹状体多巴胺（NSDA）和中脑边缘多巴胺（MLDA）神经元变性的疾病，其不包括漏斗部多巴胺（TIDA）神经元。这种易感性模式已在急性复合物I受体诱导的PD模型中得到证实，并且假定外在因素如毒素分布、生物活化、进入细胞和隔离到囊泡中是TIDA神经元抵抗的基础。在本实验中，直接暴露于鱼藤酮或1-甲基-4-苯基吡啶（MPP+）对下丘脑TIDA神经元没有影响，但显着增加中脑原代NSDA和MLDA培养物中的TIDA标记免疫反应神经元的百分比。在体内，1-甲基-4-苯基-1，2，3，6-四氢吡啶（MPTP）暴露引起含有TIDA（正中隆起[ME]）、NSDA（纹状体[ST]）和MLDA（延髓核[NA]）神经元轴突终末的脑区域中多巴胺（DA）的初始减少（4 h）。MPTP处理后16 h，ME中DA浓度恢复到对照水平，而ST和NA DA水平在MPTP处理后32 h仍较低。当小鼠和大鼠分别长期接受MPTP和鱼藤酮治疗时，出现了相同的易感性模式。TIDA神经元不受影响，而NSDA神经元遭受损失的细胞体和轴突末端DA。这些实验表明，下丘脑TDA神经元的阻力是不太可能是由于外在因素，这些神经元的内在特性的进一步研究可能阐明的机制，可以转化为神经保护策略在PD。(c)2007年IBRO。由爱思唯尔有限公司出版。保留所有权利。
Tuberoinfundibular dopamine (TIDA) neurons are spared in Parkinson's disease (PD), a disorder that causes degeneration of midbrain nigrostriatal dopamine (NSDA) and mesolimbic dopamine (MLDA) neurons. This pattern of susceptibility has been demonstrated in acute complex I inhibitor-induced models of PD, and extrinsic factors such as toxin distribution, bioactivation, entry into the cell and sequestration into vesicles are postulated to underlie the resistance of TIDA neurons. In the present experiments, direct exposure to rotenone or 1-methyl-4-phenylpyridinium (MPP+) had no effect on mediobasal hypothalamic TIDA neurons, but significantly increased the percentage of apoptag immunoreactive neurons in midbrain primary NSDA and MLDA cultures. In vivo 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) exposure caused an initial decrease (by 4 h) in dopamine (DA) in brain regions containing axon terminals of TIDA (median eminence [ME]), NSDA (striatum [ST]) and MLDA (nucleus accumbens [NA]) neurons. By 16 h after MPTP treatment, DA concentrations in ME returned to control levels, while ST and NA DA levels remained low up to 32 h after treatment with MPTP. When mice and rats were chronically treated with MPTP and rotenone, respectively, the same pattern of susceptibility emerged. TIDA neurons were unaffected while NSDA neurons suffered loss of cell bodies and axon terminal DA. These experiments demonstrate that the resistance of hypothalamic TDA neurons is not likely to be due to extrinsic factors, and that further examination of the intrinsic properties of these neurons may elucidate mechanisms that can be translated into neuroprotective strategies in PD. (c) 2007 IBRO. Published by Elsevier Ltd. All rights reserved.