کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8998463 | 1115631 | 2005 | 8 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Opposite effects of lithium and valproic acid on trophic factor deprivation-induced glycogen synthase kinase-3 activation, c-Jun expression and neuronal cell death
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
علوم اعصاب رفتاری
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Opposite effects of lithium and valproic acid on trophic factor deprivation-induced glycogen synthase kinase-3 activation, c-Jun expression and neuronal cell death Opposite effects of lithium and valproic acid on trophic factor deprivation-induced glycogen synthase kinase-3 activation, c-Jun expression and neuronal cell death](/preview/png/8998463.png)
چکیده انگلیسی
Recent studies demonstrate that lithium and valproic acid (VPA), two commonly used mood-stabilizing drugs, have neuroprotective effects against a variety of insults. Inhibition of the proapoptotic enzyme, glycogen synthase kinase-3 (GSK-3), has been suggested to be the mechanism of action of neuroprotection for both drugs. In this study, we tested if lithium and VPA could protect cultured cerebellar granule neurons (CGNs) from GSK-3-mediated apoptosis induced by trophic factor withdrawal (serum/potassium deprivation). Both lithium and indirubin, a specific GSK-3 inhibitor, protected CGNs in a dose-dependent manner. In contrast, VPA did not provide any neuroprotection and even potentiated cell death. Immunoblot analysis revealed that lithium inhibited the trophic factor deprivation-induced activation of GSK-3 as well as the in vivo phosphorylation of the microtubule-associated protein Tau on Ser199, a specific target site for GSK-3. Under these same experimental conditions, however, VPA neither inhibited GSK-3 activation nor hindered GSK-3 mediated Tau phosphorylation. Furthermore, in accordance with their effects on neuronal survival, lithium prevented the induction of c-Jun expression in trophic factor-deprived CGNs, whereas VPA potentiated it. Collectively, these results show that VPA is not a universal inhibitor of neuronal GSK-3, and that instead of being neuroprotective, VPA can even exacerbate neuronal death under some conditions.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuropharmacology - Volume 48, Issue 4, March 2005, Pages 576-583
Journal: Neuropharmacology - Volume 48, Issue 4, March 2005, Pages 576-583
نویسندگان
Ning Jin, Attila D. Kovács, Ziye Sui, Stephen Dewhurst, Sanjay B. Maggirwar,