Ethanol exposure alters neurotrophin receptor expression in the rat central nervous system: Effects of prenatal exposure.
Developmental ethanol exposure produces significant central nervous system (CNS) abnormalities. The cellular mechanisms of ethanol neurotoxicity, however, remain elusive. Recent data implicate altered neurotrophin signaling pathways in ethanol-mediated neuronal death. The present study investigated ethanol-induced alterations in neurotrophin receptor proteins in the rat CNS following chronic ethanol treatment during gestation, via liquid diet to pregnant dams. Brains were dissected on P1 and P10, and Western blots for the neurotrophin receptors TrkA, TrkB, TrkC, and p75 were quantified. Such ethanol treatment produced significant changes in neurotrophin receptor levels in the hippocampus, septum, cerebral cortex, and cerebellum. Receptor levels in hippocampus, septum, and cerebellum, tended to be decreased, while levels in cortex were consistently increased. Males were generally more affected than females. While most of these alterations were transient, sustained or delayed changes were present in P10 septum, cortex, and cerebellum. These results indicate that developmental ethanol exposure produces major changes in the normal physiological levels of the neurotrophin receptors throughout the CNS. These changes in the receptor complement during critical prenatal stages could relate to the anomalous development of the CNS seen in the fetal alcohol syndrome. This relationship is discussed, together with the potential biological effects of such dramatic changes in neurotrophin receptor expression.
Moore
D Blaine
DB
Department of Biology, Kalamazoo College, Michigan 49006-3295, USA.
Madorsky
Irina
I
Paiva
Michael
M
Barrow Heaton
Marieta
M
D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D004195:Disease Models, Animal; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000503:physiopathology; D008297:Male; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D020318:Rats, Long-Evans; D017475:Receptors, Nerve Growth Factor / Q000096:biosynthesis / Q000187:drug effects*; D012737:Sex Factors
D002492:Central Nervous System Depressants; D017475:Receptors, Nerve Growth Factor; D000431:Ethanol