title: Effects of voluntary ethanol drinking on [125I]insulin-like growth factor-I, [125I]insulin-like growth factor-II and [125I]insulin receptor binding in the mouse hippocampus and cerebellum.
abstract: Chronic exposure to ethanol can induce widespread cell loss in the brain, in some cases even causing dementia. Although the underlying mechanism associated with ethanol toxicity has not yet been established, it is suggested that one of the ways in which ethanol disrupts neuronal functioning/survival is by targeting the actions of mitogenic growth factors. Insulin-like growth factors-I and -II and insulin are structurally related polypeptides with potent mitogenic and metabolic effects on the central and peripheral nervous systems. These growth factors and their respective receptors are widely distributed throughout the brain, including the hippocampus and cerebellum. Evidence indicates that ethanol can decrease plasma levels of insulin-like growth factors and can also inhibit the growth-promoting and cell survival effects of these growth factors under in vitro conditions. The present study was designed to determine if voluntary ethanol consumption over a 21-day period could alter [125I]insulin-like growth factor-I, [125I]insulin-like growth factor-II and [125I]insulin receptor-binding sites in the hippocampus and cerebellum-areas known to be severely affected following chronic exposure to ethanol. C57BL/6 mice were presented with either water only or a choice of water and a 10% v/v ethanol solution. Mice with access to the ethanol solution drank an average of 5.35+/-0.77 g of ethanol/kg body weight per day. [125I]Insulin-like growth factor-I receptor-binding sites were found to be significantly increased in all subfields of the hippocampal formation, but not in the cerebellum, of ethanol-treated mice compared to controls. [125I]Insulin-like growth factor-II and [125I]insulin receptor-binding sites, on the other hand, did not exhibit any alterations either in the hippocampus or cerebellum following chronic exposure to ethanol. These results, in keeping with earlier reports, suggest that hippocampal insulin-like growth factor-I is more sensitive to ethanol treatment than either insulin-like growth factor-II or insulin, and the observed increase in the [125I]insulin-like growth factor-I receptor levels possibly reflects an activity-dependent response to prevent/slow down neuronal degeneration and/or to regulate subtle functional alterations that follow chronic exposure to ethanol.
authors.affiliation: Department of Neurology, Douglas Hospital Research Center, McGill University, 6875 La Salle Blvd., Québec, H4H 1R3, Verdun, Canada.
authors.forename: P W
authors.initials: PW
authors.lastname: Marinelli
authors.forename: C
authors.initials: C
authors.lastname: Gianoulakis
authors.forename: S
authors.initials: S
authors.lastname: Kar
mesh_terms: D000428:Alcohol Drinking / Q000378:metabolism*; D000818:Animals; D002492:Central Nervous System Depressants / Q000494:pharmacology; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism*; D000431:Ethanol / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D007335:Insulin-Like Growth Factor II / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011972:Receptor, Insulin / Q000378:metabolism*
chemical_list: D002492:Central Nervous System Depressants; D000431:Ethanol; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D011972:Receptor, Insulin