کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
9414637 1292051 2005 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Signaling pathways involved with serotonin1A agonist-mediated neuroprotection against ethanol-induced apoptosis of fetal rhombencephalic neurons
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب تکاملی
پیش نمایش صفحه اول مقاله
Signaling pathways involved with serotonin1A agonist-mediated neuroprotection against ethanol-induced apoptosis of fetal rhombencephalic neurons
چکیده انگلیسی
Previously, this laboratory demonstrated that developing serotonin (5-HT) neurons and other fetal rhombencephalic neurons are reduced by in vivo and in vitro exposure to ethanol, effects that are related to ethanol's augmentation of apoptosis. We also found that 5-HT1A agonists diminished the ethanol-associated reduction of 5-HT neurons and other fetal rhombencephalic neurons by attenuating the pro-apoptotic effects of ethanol. Presently, we investigated the hypothesis that the protective/anti-apoptotic effects of a 5-HT1A agonist on fetal rhombencephalic neurons are mediated by activation of the phosphatidylinositol 3′ kinase (PI-3K) and/or the mitogen-activated protein kinase kinase (MAPKK) pathway. Apoptotic and non-apoptotic fetal rhombencephalic neurons were quantitated in primary cultures that were treated with 50 mM ethanol and with 100 nM of a 5-HT1A agonist such as 8-OH-DPAT [8-hydroxy 2-(di-n-propylamino)tetralin], ipsapirone, or buspirone. Analysis of neurons stained with Hoechst 33342 demonstrated the anti-apoptotic effects of 5-HT1A agonists and implicated the involvement of the PI-3K pathway and possibly the MAPKK pathway with the protective effects of these drugs. The protective effects were blocked by a 5-HT1A antagonist (WAY 100635), an inhibitor of PI-3K (LY294002), and an inhibitor of MAPKK (PD98059). Western blot analyses showed that ethanol treatment reduces basal pAkt levels. These analyses also provide support for the involvement of the PI-3K pathway; ipsapirone stimulated the phosphorylation of Akt in control and ethanol-treated neurons, and these effects were antagonized by LY294002.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Developmental Brain Research - Volume 159, Issue 1, 8 September 2005, Pages 18-28
نویسندگان
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