Alterations of cerebellar mRNA specific for BDNF, p75NTR, and TrkB receptor isoforms occur within hours of ethanol administration to 4-day-old rat pups.
Developing cerebellar Purkinje cells of the rat are extremely sensitive to ethanol during postnatal days (PN) 4-6, but not at later times during development. Ethanol exposure during this vulnerable window induces rapid apoptotic Purkinje cell death that is hypothesized to result from ethanol inhibition in brain-derived nerve growth factor (BDNF)-TrkB neurotrophic signaling that results in loss of apoptotic suppression. In this study, the effect that different concentrations of ethanol (1.5, 3.0, 4.5 and 6.0 g/kg) have on steady-state mRNA expression of BDNF and different TrkB receptor isoforms in the cerebellum on PN4 was determined at 1, 4, 6, and 8 h after treatment. Significant decreases in mRNA specific for BDNF and TrkB isoforms were detected within 1 h after ethanol administration. No significant alterations in expression of mRNA specific to the low affinity p75(NTR) receptor were identified. These alterations are concurrent with the PN4 vulnerable period for Purkinje cells since equivalent treatment of PN9 rat pups does not produce significant alterations in mRNA specific to BDNF or TrkB at 4 h after exposure. These results support the hypothesis that ethanol induces a disruption of BDNF-TrkB signaling that results in loss of apoptotic suppression in vulnerable Purkinje cells by growth factor withdrawal.
Ge
Yun
Y
Department of Pharmacology and Toxicology, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
Belcher
Scott M
SM
Light
Kim E
KE
D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D002531:Cerebellum / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D008297:Male; D011247:Pregnancy; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020800:Receptor, Nerve Growth Factor; D020813:Receptor, trkB / Q000235:genetics / Q000378:metabolism*; D017475:Receptors, Nerve Growth Factor / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013997:Time Factors
D019208:Brain-Derived Neurotrophic Factor; D002492:Central Nervous System Depressants; D012333:RNA, Messenger; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor; D000431:Ethanol; D020813:Receptor, trkB