The effects of perinatal choline supplementation on hippocampal cholinergic development in rats exposed to alcohol during the brain growth spurt
| Autor: | Frances M. Leslie, Bradley R. Monk, Jennifer D. Thomas |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Male
medicine.medical_specialty Cognitive Neuroscience Hippocampus Hippocampal formation Article Open field Choline Rats Sprague-Dawley chemistry.chemical_compound Pregnancy Internal medicine Muscarinic acetylcholine receptor Animals Humans Medicine Receptor Muscarinic M2 Behavior Animal Ethanol Receptor Muscarinic M4 business.industry Receptor Muscarinic M1 Receptors Muscarinic Acetylcholine Rats Endocrinology Animals Newborn chemistry Fetal Alcohol Spectrum Disorders Prenatal Exposure Delayed Effects Dietary Supplements Cholinergic Female business Neuroscience Choline chloride medicine.drug |
| Zdroj: | Hippocampus. 22:1750-1757 |
| ISSN: | 1050-9631 |
| DOI: | 10.1002/hipo.22009 |
| Popis: | Prenatal alcohol exposure leads to long-lasting cognitive and attention deficits, as well as hyperactivity. Using a rat model, we have previously shown that perinatal supplementation with the essential nutrient, choline, can reduce the severity of some fetal alcohol effects, including hyperactivity and deficits in learning and memory. In fact, choline can mitigate alcohol-related learning deficits even when administered after developmental alcohol exposure, during the postnatal period. However, it is not yet known how choline is able to mitigate alcohol-related behavioral alterations. Choline may act by altering cholinergic signaling in the hippocampus. This study examined the effects of developmental alcohol exposure and perinatal choline supplementation on hippocampal M(1) and M(2/4) muscarinic receptors. Sprague-Dawley rat pups were orally intubated with ethanol (5.25 mg/kg/day) from postnatal days (PD) 4-9, a period of brain development equivalent to the human third trimester; control subjects received sham intubations. From PD 4-30, subjects were injected s.c. with choline chloride (100 mg/kg/day) or saline vehicle. Open field activity was assessed from PD 30 through 33, and brain tissue was collected on PD 35 for autoradiographic analysis. Ethanol-exposed subjects were more active compared to controls during the first 2 days of testing, an effect attenuated with choline supplementation. Developmental alcohol exposure significantly decreased the density of muscarinic M(1) receptors in the dorsal hippocampus, an effect that was not altered by choline supplementation. In contrast, developmental alcohol exposure significantly increased M(2/4) receptor density, an effect mitigated by choline supplementation. In fact, M(2/4) receptor density of subjects exposed to alcohol and treated with choline did not differ significantly from that of controls. These data suggest that developmental alcohol exposure can cause long-lasting changes in the hippocampal cholinergic system and that perinatal choline supplementation may attenuate alcohol-related behavioral changes by influencing cholinergic systems. |
| Databáze: | OpenAIRE |
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