Signaling pathways involved with serotonin1A agonist-mediated neuroprotection against ethanol-induced apoptosis of fetal rhombencephalic neurons
| Autor: | Nuzhath F. Tajuddin, Mary J. Druse, Roberta A. Gillespie, Phong T. Le |
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| Rok vydání: | 2005 |
| Předmět: |
Agonist
MAPK/ERK pathway Serotonin medicine.drug_class Apoptosis Biology Nervous System Malformations Neuroprotection Rats Sprague-Dawley chemistry.chemical_compound Developmental Neuroscience Pregnancy medicine Animals LY294002 Enzyme Inhibitors Protein kinase A Protein kinase B Cells Cultured Neurons Ethanol Ipsapirone Serotonin 5-HT1 Receptor Agonists Cell biology Rats Serotonin Receptor Agonists Rhombencephalon Disease Models Animal Neuroprotective Agents nervous system chemistry Cytoprotection Fetal Alcohol Spectrum Disorders Receptor Serotonin 5-HT1A Raphe Nuclei Female Serotonin Antagonists Signal transduction Developmental Biology medicine.drug Signal Transduction |
| Zdroj: | Brain research. Developmental brain research. 159(1) |
| ISSN: | 0165-3806 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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