TUNEL-positive cells in the substantia nigra of C57BL/6 mice after a single bolus of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.

TUNEL-positive cells in the substantia nigra of C57BL/6 mice after a single bolus of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.
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单次推注 1-甲基-4-苯基-1,2,3,6-四氢吡啶后,C57BL/6 小鼠黑质中的 TUNEL 阳性细胞。

DOI:
10.1016/s0306-4522(97)00640-4
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发表时间:
1998
期刊:
影响因子:
3.3
通讯作者:
C. Wiessner
C. Wiessner
中科院分区:
医学3区
文献类型:
--
作者:
W. Spooren;C. Gentsch;C. Wiessner

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使用末端脱氧核苷酸转移酶介导的dUTP生物素缺口末端标记(TUNEL染色)作为组织化学标记物,研究了1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)诱导的黑质细胞死亡中细胞凋亡的参与情况。单剂MPTP。在注射后第3天,但不是第1和第7天,单次皮下注射MPTP(50 mg/kg)后,TUNEL阳性细胞的数量显着增加,显示出典型的凋亡形态。这些数据表明,即使在单次MPTP注射后,黑质中的至少部分细胞也通过程序性细胞死亡而死亡。因此,应用(亚)慢性MPTP中毒来诱导黑质中的细胞凋亡不是强制性的。MPTP,即选择性地影响黑质中的多巴胺能神经元的神经毒素,在人和动物中诱导与帕金森病非常相似的症状。4,6,7 1-甲基-4-吡啶鎓(MPP+),即MPTP的毒性代谢产物,通过多巴胺再摄取系统在神经末梢水平被黑质神经元摄取,随后进入线粒体。MPP+抑制呼吸链的复合物I,诱导ATP消耗,最终导致细胞死亡。
The involvement of apoptosis in 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine(MPTP)-induced cell death in the substantia nigra was investigated using terminal deoxynucleotidyl transferase-mediated dUTP biotin nick-end labelling (TUNEL staining) as a histochemical marker after a single bolus of MPTP. A significant increase in the number of TUNEL-positive cells showing a typical apoptotic morphology was found at post-injection day 3, but not 1 and 7, following a single subcutaneous MPTP (50 mg/kg) injection. These data suggest that at least part of the cells in the substantia nigra die via programmed cell death even after a single MPTP injection. Thus it is not obligatory to apply a (sub-) chronic MPTP intoxication to induce apoptosis in the substantia nigra.MPTP, ie a neurotoxin that selectively affects dopaminergic neurons in the substantia nigra, induces symptoms in man and animal closely resembling Parkinson’s disease. 4, 6, 7 1-Methyl-4-pyridinium (MPP+), ie MPTP’s toxic metabolite, is taken up into nigral neurons at the nerve terminal level via the dopamine re-uptake system and subsequently gains entrance into mitochondria. 7, 9 There MPP+ inhibits complex I of the respiration chain inducing ATP depletion which finally leads to cell