Excitotoxicity caused by ethanol (ETOH) withdrawal (EWD) is highly detrimental to the developing brain. Targeting this excitotoxicity has been shown to be a promising approach for improving outcome following developmental ETOH exposure. Activation of nicotinic acetylcholine receptors (nAChR), in the central nervous system can be protective against EWD. We examined the ability of DMXB-A, a α7 nAChR agonist, to reduce neurotoxicity caused by EWD in the hippocampus. To test this, an organotypic hippocampal slice culture was used. Slices were exposed to ETOH (100mM) or control medium. After 10 days, the slices were treated with DMXB-A (1, 3, or 10uM) during EWD. After 24 hours of EWD cell damage in the CA1, CA3, and dentate gyrus of the hippocampus was analyzed. The combination of EWD and NMDA produced increased toxicity compared to controls in the CA1 region, DMXB-A attenuated this effect, suggesting that DMXB-A was protective against EWD neurotoxicity in vitro. These findings are exciting because this drug is currently in clinical trials for a variety of CNS conditions and so has significant translational potential. Further research is necessary to better understand the extent of its neuroprotective properties and to determine its ability to reduce behavioral deficits following prenatal ethanol exposure.
| Identifer | oai:union.ndltd.org:uky.edu/oai:uknowledge.uky.edu:psychology_etds-1084 |
| Date | 01 January 2015 |
| Creators | Fields, Logan J. |
| Publisher | UKnowledge |
| Source Sets | University of Kentucky |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | Theses and Dissertations--Psychology |
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