کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
6804719 | 1433558 | 2015 | 8 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Effects of aging on glutamate neurotransmission in the substantia nigra of Gdnf heterozygous mice
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
سالمندی
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چکیده انگلیسی
Glial cell line-derived neurotrophic factor (GDNF) helps protect dopaminergic neurons in the nigrostriatal tract. Although the cause of nigrostriatal degeneration is unknown, one theory is that excess glutamate from the subthalamic nucleus results in excitotoxic events in the substantia nigra (SN). Because dopaminergic degeneration is accompanied by a reduction in GDNF, we examined glutamate neurotransmission in the SN using a Gdnf heterozygous mouse model (Gdnf+/â) at 8 and 12Â months of age. At 8Â months, Gdnf+/â mice have greater glutamate release and higher basal glutamate levels, which precede the SN dopaminergic degeneration observed at 12Â months of age. However, at 12Â months, Gdnf+/â mice have lower basal levels of glutamate and less glutamate release than wild-type mice. Also at 8Â months, Gdnf+/â mice have lower levels of glutamate transporter-1 and greater glial fibrillary acidic protein levels in the SN compared with wild-type mice, differences that increase with age. These data suggest that reduced levels of GDNF induce excess glutamate release and dysregulation of glutamate transporter-1, causing excitotoxicity in the SN that precedes dopaminergic degeneration.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neurobiology of Aging - Volume 36, Issue 3, March 2015, Pages 1569-1576
Journal: Neurobiology of Aging - Volume 36, Issue 3, March 2015, Pages 1569-1576
نویسندگان
Ariana Q. Farrand, Rebecca A. Gregory, Michael D. Scofield, Kristi L. Helke, Heather A. Boger,