The effects of chronic ethanol consumption on neurotrophins and their receptors in the rat hippocampus and basal forebrain.
Damage to the basal forebrain frequently results in deficits in learning and memory. Mnenonic dysfunction also occurs following prolonged ethanol consumption in humans and in animal models of chronic ethanol intake, accompanied by specific abnormalities in synaptic transmission between the basal forebrain and hippocampus. The integrity of at least some of the reciprocal neuronal connections between these brain regions is influenced by target-derived neurotrophic factors. We used a semiquantitative reverse transcription polymerase chain reaction technique to measure the messenger RNA for neurotrophins BDNF and NGF, and for their receptors trkB, trkA, and the low affinity receptor, p75(NTR) in the hippocampus and basal forebrain of rats after 28 weeks of alcohol consumption without malnutrition. This chronic ethanol treatment (CET) resulted in a marked and selective reduction in basal forebrain trkA mRNA. Western blotting revealed a similar reduction of basal forebrain trkA protein. CET effects on basal forebrain trkA may reflect impaired NGF signaling that could compromise septohippocampal synaptic connections, cholinergic differentiation, and emergent functional abilities dependent on these properties.
Miller
R
R
Department of Neuroscience and McKnight Brain Institute, Box 100244 JHMHC, University of Florida College of Medicine, Gainesville, FL 32610-0244, USA. rehae@ufbi.ufl.edu
King
M A
MA
Heaton
M B
MB
Walker
D W
DW
D000428:Alcohol Drinking / Q000378:metabolism; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D000431:Ethanol / Q000008:administration & dosage*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D016548:Prosencephalon / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D020318:Rats, Long-Evans; D020800:Receptor, Nerve Growth Factor; D020917:Receptor, trkA / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D020813:Receptor, trkB / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D017475:Receptors, Nerve Growth Factor / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*
D019208:Brain-Derived Neurotrophic Factor; D012333:RNA, Messenger; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor; D000431:Ethanol; D020917:Receptor, trkA; D020813:Receptor, trkB