Apoptotic mode of cell death in substantia nigra following intranigral infusion of the parkinsonian neurotoxin, MPP+ in sprague-dawley rats:: Cellular, molecular and ultrastructural evidences

被引:11
作者
Banerjee, Rebecca [1 ]
Sreetama, Sen [1 ]
Saravanan, Karuppagounder S. [1 ]
Dey, Sailendra Nath [1 ]
Mohanakumar, Kochupurackal P. [1 ]
机构
[1] Indian Inst Chem Biol, Lab Clin & Expt Neurosci, Div Cell Biol & Physiol, Kolkata 700032, W Bengal, India
关键词
dopaminergic neurodegeneration; nuclear morphology; nuclear ultrastructure; internucleosomal fragmentation; substantia nigra pars compacta; tyrosine hydroxylase positive neurons; condensed chromatin; Parkinson's disease; INDUCED DOPAMINERGIC NEUROTOXICITY; 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE MPTP; TYROSINE-HYDROXYLASE; NEURONAL APOPTOSIS; N-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE; 1-METHYL-4-PHENYLPYRIDINIUM; DISEASE; METABOLITE; TOXICITY; EFFECTOR;
D O I
10.1007/s11064-007-9299-8
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The potent parkinsonian neurotoxin 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) is known to cause dopaminergic neurodegeneration in nigrostriatal system. In the present study we investigated the nuclear morphology of cells in the substantia nigra pars compacta (SNpc) region of rats following unilateral intranigral infusion of the active metabolite, 1-methyl-4-phenyl pyridinium ion (MPP+), which resulted in a dose-dependent and prolonged dopamine depletion in the ipsilateral striatum. There appeared a substantial loss of tyrosine hydroxylase immunoreactive neurons in the SNpc that received the neurotoxin. Specific nuclear staining with Hoechst 33342 or acridine orange revealed bright pyknotic, shrunken, distorted nuclei and condensed chromatin with perinuclear nucleolus respectively following visualization with the former and latter dyes in the ipsilateral SNpc, as compared to the round, intact nuclei and centrally positioned nucleolus in the contralateral side. Ultrastructural details of the nucleus under transmission electron microscope confirmed distorted nuclear organization with shrunken or condensed nuclei and disrupted nuclear membrane. These features are typical of nucleus undergoing apoptosis, and suggest that MPP+ causes dopaminergic neuronal death through an apoptotic mode. Typical laddering pattern of genomic DNA isolated from the ipsilateral SN in agarose gel electrophoresis conclusively established apoptosis following intranigral administration of MPP+ in rats.
引用
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页码:1238 / 1247
页数:10
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