Neg, a nerve growth factor-stimulated gene expressed by fetal neocortical neurons that is downregulated by ethanol.
Neurotrophins are critical for neuronal development, plasticity, and survival. Ethanol affects these processes. We tested the hypothesis that ethanol inhibits nerve growth factor (NGF)-stimulated gene expression. Dissociated cultures of fetal cortical neurons were treated with NGF and/or ethanol. NGF sustained cell viability and reduced the incidence of terminal uridylated nick-end labeling and pyknosis. Ethanol eliminated these effects and induced neuronal death. Differential display of mRNA showed that one gene fragment (245 bp) was expressed by cells treated with NGF alone; ethanol blocked its expression. This fragment, named neg (nerve growth factor-stimulated, ethanol-depressed gene), has high nucleotide identity with genes from human myeloid cells and murine lymphocytes. Ribonuclease protection assay and in situ hybridization verified NGF upregulation and ethanol antagonism. Thus, ethanol specifically alters the expression of a gene that appears to be involved in NGF-mediated neuroprotection.
Miller
Michael W
MW
Department of Neuroscience and Physiology, State University of New York, Upstate Medical University, Syracuse, New York 13210, USA. millermw@upstate.edu
Jacobs
Julie S
JS
Yokoyama
Ruth
R
D000595:Amino Acid Sequence / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001483:Base Sequence / Q000187:drug effects / Q000502:physiology; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D005333:Fetus / Q000187:drug effects* / Q000196:embryology / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000502:physiology; D008969:Molecular Sequence Data; D019579:Neocortex / Q000187:drug effects* / Q000196:embryology / Q000378:metabolism; D020932:Nerve Growth Factor / Q000096:biosynthesis*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D011247:Pregnancy; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley
D012333:RNA, Messenger; D000431:Ethanol; D020932:Nerve Growth Factor