Ethanol exposure alters neurotrophin receptor expression in the rat central nervous system: Effects of neonatal exposure.
The detrimental effects of ethanol exposure during nervous system development have been well established. The cellular mechanisms of ethanol neurotoxicity, however, have not been clearly defined. Recent studies suggest that neurotrophin signaling pathways may be involved in ethanol-mediated neuronal death. The present investigation, therefore, was designed to examine ethanol-induced alterations in neurotrophin receptor protein levels in the developing central nervous system (CNS) following chronic ethanol treatment administered during the early neonatal period. For this study, rats were exposed to ethanol via vapor inhalation from postnatal day 4 (P4) to P10. Brains were then dissected on P10 or P21, and Western blots used to quantify expression of neurotrophin receptors TrkA, TrkB, TrkC, and p75. This early postnatal ethanol treatment produced significant alterations in receptor levels in hippocampus, septum, cerebral cortex, and cerebellum. The alterations seen were variable, with decreases generally found in hippocampus and cerebellum, increases noted in septum, and changes in both directions occurring in cortex. These alterations were generally more prevalent in males than in females. While most of the receptor changes observed were transient, sustained or delayed alterations were occasionally seen in hippocampus, cortex, and cerebellum. These results suggest that developmental ethanol exposure modulates expression of these neurotrophin receptors throughout the CNS, alterations which could have wide-ranging effects on functional CNS development. The possible linkage between such changes and abnormalities encountered in the fetal alcohol syndrome are considered.
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; D000831:Animals, Newborn; 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; D051381:Rats; 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