Ethanol reduces expression of the nerve growth factor receptor, but not nerve growth factor protein levels in the neonatal rat cerebellum.
The cerebellum is especially vulnerable to ethanol's neurotoxic effects during development, and ethanol exposure during the brain growth spurt will deplete cerebellar neurons. The mechanisms undertying this neuronal cell loss remain elusive. Nerve growth factor (NGF) is a neurotrophin that promotes cell survival in various brain areas, and there is evidence that NGF may play a role in the developing cerebellum. This study examined whether ethanol exposure of the neonatal rat cerebellum altered the levels of either NGF or the expression of p75 and trkA, which are two components of the NGF receptor. Ethanol exposure had no effect on NGF levels in the neonatal cerebellum, as determined by an NGF-specific ELISA. Immunohistochemical labeling techniques indicated that both the p75 and trkA NGF receptors were expressed on Purkinje cell dendrites in the developing cerebellum, with posterior lobules expressing higher levels of p75 and trkA NGF receptor, compared with anterior lobules. Ethanol exposure of neonatal rats reduced the expression of both p75 and trkA NGF receptors on the Purkinje cell dendrites. These results suggest that ethanol could interfere with neurotrophic support of Purkinje cells by reducing the levels of available NGF receptor.
Dohrman
D P
DP
Neuroscience Program, College of Medicine, University of Iowa, Iowa City 52242, USA.
West
J R
JR
Pantazis
N J
NJ
D000818:Animals; D001931:Brain Mapping; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002531:Cerebellum / Q000187:drug effects* / Q000473:pathology; D000431:Ethanol / Q000633:toxicity*; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000473:pathology*; D008297:Male; D009414:Nerve Growth Factors / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D011247:Pregnancy; D011518:Proto-Oncogene Proteins / Q000187:drug effects / Q000502:physiology; D011689:Purkinje Cells / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020794:Receptor Protein-Tyrosine Kinases / Q000187:drug effects / Q000502:physiology; D020800:Receptor, Nerve Growth Factor; D020917:Receptor, trkA; D017475:Receptors, Nerve Growth Factor / Q000187:drug effects* / Q000502:physiology
D009414:Nerve Growth Factors; D011518:Proto-Oncogene Proteins; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor; D000431:Ethanol; D020794:Receptor Protein-Tyrosine Kinases; D020917:Receptor, trkA