کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
6277608 1295769 2010 16 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Prosurvival effect of human wild-type α-synuclein on MPTP-induced toxicity to central but not peripheral catecholaminergic neurons isolated from transgenic mice
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب (عمومی)
پیش نمایش صفحه اول مقاله
Prosurvival effect of human wild-type α-synuclein on MPTP-induced toxicity to central but not peripheral catecholaminergic neurons isolated from transgenic mice
چکیده انگلیسی
In the present work we report the generation of a new line of α-synuclein (α-SYN) transgenic mice in which the human wild-type α-SYN cDNA is expressed under the control of a tyrosine hydroxylase (TH) promoter. We provide evidence that the ectopic protein is found in TH expressing neurons of both central and peripheral nervous systems. The transgene is expressed very early in development coinciding with the activity of the TH promoter and in the adult brain the human protein distributes normally to the nerve endings and cell bodies of dopaminergic nigral neurons without any evidence of abnormal aggregation. Our results indicate that expression of human wild-type α-SYN does not affect normal development or maintenance of TH immunoreactive nigral neurons, striatal dopamine content, or locomotor activity. Systemic administration of the parkinsonian neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induces a loss of TH immunoreactive nigral neurons and terminals and of dopamine levels to the same degree in both transgenic and non-transgenic adult mice. Intoxication also results in a similar loss of cardiac noradrenaline in both genotypes. Surprisingly, cultured transgenic ventral mesencephalic fetal dopaminergic neurons exhibit complete resistance to cell death induced by 1-methyl-4-phenylpyridinium ion (MPP+) intoxication, without changes in dopamine transporter (DAT) surface levels. Interestingly, this protection is not observed in other populations of catecholaminergic neurons such as peripheral sympathetic neurons, despite their high sensitivity to MPP+in vitro.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuroscience - Volume 167, Issue 2, 5 May 2010, Pages 261-276
نویسندگان
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