title: Nerve growth factor and chronic ethanol treatment alter calcium homeostasis in developing rat septal neurons.
abstract: Chronic ethanol treatment (CET) during development produces cellular adaptations resulting in tolerance to the acute effects of ethanol (EtOH). The objectives of this study were to determine whether CET during the prenatal period (PCET) followed by a period of in vitro CET (PCET-CET) altered intracellular calcium [Ca(2+)](i) and produced tolerance to acute EtOH treatment (AET), and whether nerve growth factor (NGF) modulated the effects of PCET-CET in cultured developing rat septal neurons. Fetuses were obtained from EtOH-fed and sucrose-fed (diet-control) female rats. Neurons from PCET fetuses were cultured in the presence of NGF (+NGF) and 200 mg/dl (mg %) EtOH and diet-control cultures received NGF and no EtOH. PCET and diet-control cultures were then divided into two groups, +NGF and -NGF (withdrawn from NGF), and exposed acutely to one of five doses of EtOH during stimulation with potassium (K(+)) chloride. [Ca(2+)](i) was measured using fura-2. PCET-CET did not affect resting [Ca(2+)](i). PCET-CET decreased and acute EtOH withdrawal increased overall K(+)-stimulated changes in [Ca(2+)](i), but only in +NGF PCET neurons. Reducing the level of EtOH from 200 to 100 mg % decreased overall K(+)-stimulated [Ca(2+)](i) in -NGF PCET neurons. The effects of PCET-CET or PCET-CET combined with NGF on overall K(+)-stimulated changes in [Ca(2+)](i) occurred mostly in the early and middle phases of the K(+)-response. NGF reduced overall K(+)-stimulated changes in [Ca(2+)](i) in PCET neurons during EtOH withdrawal and during AET with 200 mg % EtOH and increased overall K(+)-stimulated changes in [Ca(2+)](i) during AET with 400 and 800 mg % EtOH. There was no effect of NGF on overall K(+)-stimulated changes in [Ca(2+)](i) in diet-control neurons with the exception that NGF-treatment decreased overall K(+)-stimulated changes in [Ca(2+)](i) during AET with 400 mg % EtOH. The effects of AET on overall K(+)-stimulated changes in [Ca(2+)](i) mostly occurred in +NGF PCET neurons. In conclusion, CET during development of the brain could adversely affect Ca(2+)-dependent functions such as neuronal migration, neurite outgrowth, and synaptogenesis in neurons even in the presence of neurotrophin support.
authors.affiliation: Department of Neuroscience, Center for Alcohol Research, Gainesville, FL, USA.
authors.forename: Barbara
authors.initials: B
authors.lastname: Webb
authors.forename: Don W
authors.initials: DW
authors.lastname: Walker
authors.forename: Marieta B
authors.initials: MB
authors.lastname: Heaton
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000502:physiology*; D002478:Cells, Cultured; D002492:Central Nervous System Depressants / Q000494:pharmacology; D004032:Diet / Q000379:methods; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004622:Embryo, Mammalian; D000431:Ethanol / Q000032:analysis / Q000494:pharmacology*; D005260:Female; D016257:Fura-2 / Q000493:pharmacokinetics; D006706:Homeostasis / Q000187:drug effects* / Q000502:physiology; D008297:Male; D020932:Nerve Growth Factor / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D011188:Potassium / Q000494:pharmacology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D020665:Septum of Brain / Q000187:drug effects* / Q000502:physiology; D013997:Time Factors; D028761:Withholding Treatment
chemical_list: D002492:Central Nervous System Depressants; D000431:Ethanol; D020932:Nerve Growth Factor; D011188:Potassium; D002118:Calcium; D016257:Fura-2