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The effects of ethanol and the serotonin(1A) agonist ipsapirone on the expression of the serotonin(1A) receptor and several antiapoptotic proteins in fetal rhombencephalic neurons.

Authors: Druse, MJ  Tajuddin, NF  Gillespie, RA  Le, P 
Citation: Druse MJ, etal., Brain Res. 2006 May 30;1092(1):79-86. Epub 2006 May 9.
Pubmed: (View Article at PubMed) PMID:16687129
DOI: Full-text: DOI:10.1016/j.brainres.2006.02.065

Previously, this laboratory demonstrated that ethanol reduces the number of developing serotonin (5-HT)-containing neurons by increasing apoptosis. We also found that 5-HT(1A) agonists attenuate the proapoptotic effects of ethanol and the ethanol-mediated reduction of fetal 5-HT neurons. These neuroprotective effects are mediated in part by the ability of 5-HT(1A) agonists to activate the phosphatidyl 3'-kinase (PI-3K) prosurvival pathway. NF-kappaB is one of the downstream effectors activated by this pathway. In the present study, we used quantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR) to determine the effects of 50mM ethanol and 100nM of ipsapirone, a 5-HT(1A) agonist, on the expression of several NF-kappaB-dependent antiapoptotic genes: X-linked inhibitor of apoptosis protein (XIAP), cIAP1, cIAP2, Bcl-2, and Bcl-xl. We also investigated the effects of ethanol and ipsapirone on the expression of the gene encoding the 5-HT(1A) receptor. The results demonstrate that ethanol reduces the expression of several prosurvival genes: XIAP, cIAP1, cIAP2, Bcl-2, and Bcl-xl. Importantly, the ethanol-mediated reduction in the expression of XIAP and Bcl-xl was prevented by co-treatment with ipsapirone. Thus, the damaging effects of ethanol are likely to involve a reduction in several prosurvival proteins. Moreover, the protective effects of ipsapirone on ethanol-treated neurons might involve their ability to prevent the reduction of XIAP and Bcl-xl. Although ipsapirone treatment decreased the expression of cIAP1, Bcl-2, and Bcl-xl in control neurons, our prior studies suggest that their survival is not reduced by ipsapirone. We also observed an increased expression of the 5-HT(1A) receptor in ipsapirone-treated control neurons.

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CRRD Object Information
CRRD ID: 1643530
Created: 2008-01-11
Species: All species
Last Modified: 2008-01-11
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.