Opposing effects of ethanol and nicotine on hippocampal calbindin-D28k expression
| Autor: | Patrick J. Mulholland, Rachel L. Self, Lincoln H. Wilkins, John M. Littleton, Mark A. Prendergast, Robert C. Holley, Barton R. Harris, John A. Blanchard |
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| Rok vydání: | 2003 |
| Předmět: |
Male
medicine.medical_specialty Calbindins Nicotine Health (social science) Hippocampal formation Toxicology Biochemistry Hippocampus Rats Sprague-Dawley Behavioral Neuroscience chemistry.chemical_compound S100 Calcium Binding Protein G Internal medicine medicine Animals Acetylcholine receptor Methyllycaconitine Ethanol Dose-Response Relationship Drug Antagonist Neurotoxicity General Medicine medicine.disease Rats Substance Withdrawal Syndrome Endocrinology Nicotinic agonist nervous system Neurology chemistry Gene Expression Regulation Calbindin 1 Female medicine.drug |
| Zdroj: | Alcohol (Fayetteville, N.Y.). 31(1-2) |
| ISSN: | 0741-8329 |
| Popis: | Long-term ethanol exposure produces multiple neuroadaptations that likely contribute to dysregulation of Ca2+ balance and neurotoxicity during ethanol withdrawal. Conversely, nicotine exposure may reduce the neurotoxic consequences of Ca2+ dysregulation, putatively through up-regulation of the Ca2+-buffering protein calbindin-D28k. The current studies were designed to examine the extent to which 10-day ethanol exposure and withdrawal altered calbindin-D28k expression in rat hippocampus. Further, in these studies, we examined the ability of nicotine, through action at α 7 ∗ -bearing nicotinic acetylcholine receptors (nAChRs), to antagonize the effects of ethanol exposure on calbindin-D28k expression. Organotypic cultures of rat hippocampus were exposed to ethanol (50–100 mM) for 10 days. Additional cultures were exposed to 500 nM (–)-nicotine with or without the addition of 50 mM ethanol, 100 nM methyllycaconitine (an α 7 ∗ -bearing nAChR antagonist), or both. Prolonged exposure to ethanol (≥50 mM) produced significant reductions of calbindin-D28k immunolabeling in all regions of the hippocampal formation, even at nontoxic concentrations of ethanol. Calbindin-D28k expression levels returned to near-control levels after 72 h of withdrawal from 10-day ethanol exposure. Extended (–)-nicotine exposure produced significant elevations in calbindin-D28k expression levels that were prevented by methyllycaconitine co-exposure. Co-exposure of cultures to (–)-nicotine with ethanol resulted in an attenuation of ethanol-induced reductions in calbindin-D28k expression levels. These findings support the suggestion that long-term ethanol exposure reduces the neuronal capacity to buffer accumulated Ca2+ in a reversible manner, an effect that likely contributes to withdrawal-induced neurotoxicity. Further, long-term exposure to (–)-nicotine enhances calbindin-D28k expression in an α 7 ∗ nAChR–dependent manner and antagonizes the effects of ethanol on calbindin-D28k expression. |
| Databáze: | OpenAIRE |
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