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Effects of ethanol and transforming growth factor beta (TGF beta) on neuronal proliferation and nCAM expression
1Department of Neuroscience and Physiology, State University of New York-Upstate Medical University, 750 East Adams Street, Syracuse, NY 13210, USA. millermw@upstate.edu
Abstract:
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.
Insights
Transforming growth factor beta1 (TGFβ1) and ethanol both inhibit neuronal proliferation. While TGFβ1 and ethanol up-regulate neural cell adhesion molecule (nCAM) expression, ethanol blocks TGFβ1
Area of Science:
- Neuroscience
- Developmental Biology
- Toxicology
Background:
- Ethanol impacts neuronal development, including cell proliferation, migration, and neurite outgrowth.
- Neural cell adhesion molecule (nCAM) mediates neuronal migration and outgrowth.
- Transforming growth factor beta1 (TGFβ1) influences these critical developmental events.
Purpose of the Study:
- To investigate the effects of ethanol on TGFβ1-mediated activities in developing cortical neurons.
- To examine the interplay between ethanol and TGFβ1 in regulating neuronal proliferation and nCAM expression.
Main Methods:
- Primary cultures of cortical neurons from 16-day-old fetal rats were utilized.
- Neurons were treated with varying concentrations of TGFβ1 and ethanol for 48 hours.
- Cell numbers, [³H]thymidine incorporation, and nCAM expression were quantified.
Main Results:
- Both TGFβ1 and ethanol exhibited anti-mitogenic effects, inhibiting cell growth and proliferation additively.
- TGFβ1 and ethanol independently promoted the expression of multiple nCAM isoforms.
- Ethanol interfered with TGFβ1-induced nCAM expression, particularly for 120 and 180 kDa isoforms.
Conclusions:
- TGFβ1 ligands inhibit neuronal proliferation and enhance cell adhesion molecule expression, facilitating neuronal movement and outgrowth.
- Ethanol also modulates these developmental processes, affecting neuronal proliferation and nCAM expression.
- Potential interactions between TGFβ1 and ethanol in neuronal development warrant further investigation.