PMID- 12198406 OWN - NLM STAT- MEDLINE DCOM- 20030203 LR - 20131121 IS - 0145-6008 (Print) IS - 0145-6008 (Linking) VI - 26 IP - 8 DP - 2002 Aug TI - Effects of ethanol and transforming growth factor beta (TGF beta) on neuronal proliferation and nCAM expression. PG - 1281-5 AB - BACKGROUND Developmental events targeted by ethanol are cell proliferation, neuronal migration, and neurite outgrowth; the latter processes being mediated by neural cell adhesion molecule (nCAM). TGFbeta1 affects all three of these events. Therefore, the effects of ethanol on transforming growth factor (TGF) beta1 mediated activities in neocortical neurons in vitro were examined. METHODS Primary cultures of cortical neurons were obtained from 16-day-old fetuses and were treated with TGFbeta1 (0 or 10 ng/ml) and ethanol (0 or 400 mg/dl) for 48 hr. The effects of these substances on cell numbers, [ H]thymidine incorporation, and the expression of nCAM were determined. RESULTS Both cell growth (the change in cell numbers over time) and cell proliferation were inhibited by TGFbeta1 and ethanol. The action of these two anti-mitogenic factors was additive. In contrast, TGFbeta1 also promoted the expression of three isoforms of nCAM. Likewise, ethanol also up-regulated nCAM expression. On the other hand, ethanol blocked TGFbeta1-mediated nCAM expression, particularly of the 120 and 180 kDa isoforms. CONCLUSIONS TGFbeta ligands inhibit neuronal proliferation and stimulate the expression of cell adhesion proteins that promote the movement of postmitotic neurons and process outgrowth. Ethanol alters these phenomena as well. Thus, in neurons, as in astrocytes, TGFbeta1 and ethanol may interact. FAU - Miller, Michael W AU - Miller MW AD - Department of Neuroscience and Physiology, State University of New York-Upstate Medical University, 750 East Adams Street, Syracuse, NY 13210, USA. millermw@upstate.edu FAU - Luo, Jia AU - Luo J LA - eng GR - AA 06916/AA/NIAAA NIH HHS/United States GR - AA 07568/AA/NIAAA NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, Non-P.H.S. PT - Research Support, U.S. Gov't, P.H.S. PL - England TA - Alcohol Clin Exp Res JT - Alcoholism, clinical and experimental research JID - 7707242 RN - 0 (Growth Inhibitors) RN - 0 (Neural Cell Adhesion Molecules) RN - 0 (Protein Isoforms) RN - 0 (Transforming Growth Factor beta) RN - 3K9958V90M (Ethanol) SB - IM MH - Animals MH - Cell Division/drug effects/physiology MH - Cells, Cultured MH - Cerebral Cortex/cytology/drug effects/metabolism MH - Embryo, Mammalian MH - Ethanol/*pharmacology MH - Female MH - Growth Inhibitors/*pharmacology/*physiology MH - Neural Cell Adhesion Molecules/*biosynthesis MH - Neurons/cytology/*drug effects/metabolism MH - Pregnancy MH - Protein Isoforms/biosynthesis MH - Rats MH - Transforming Growth Factor beta/pharmacology/*physiology MH - Up-Regulation/drug effects EDAT- 2002/08/29 10:00 MHDA- 2003/02/04 04:00 CRDT- 2002/08/29 10:00 PHST- 2002/08/29 10:00 [pubmed] PHST- 2003/02/04 04:00 [medline] PHST- 2002/08/29 10:00 [entrez] AID - 10.1097/01.ALC.0000026836.38681.58 [doi] PST - ppublish SO - Alcohol Clin Exp Res. 2002 Aug;26(8):1281-5. doi: 10.1097/01.ALC.0000026836.38681.58.