Reversal of ethanol toxicity in embryonic neurons with growth factors and estrogen.
Prenatal exposure to ethanol is the cause of fetal alcohol syndrome, which is characterized by brain abnormalities and decreased mental capacity. In the current study, cultured neurons from embryonic rat cortices were used to study the reversal of ethanol toxicity on neuronal survival and neurite outgrowth. Ethanol treatment followed by treatment with estrogen and certain growth factors were used to assess the potential of these growth factors and estrogen to reverse the effects of ethanol damage. Cortical neurons from embryonic day (E) 16 rats were grown in defined medium with a glial plane at a distance of 1mm from the neurons. Ethanol (45 mM) was administered on day in vitro 1 (DIV 1) and DIV 4. Insulin-like growth factor-I (IGF-I, 10 ng/ml), insulin-like growth factor-II (IGF-II, 10 ng/ml), basic fibroblast growth factor (bFGF, 5 ng/ml), nerve growth factor (NGF, 100 ng/ml), and estrogen (Es, 10 ng/ml) were administered on DIV 4 and DIV 5. Cell viability was determined on DIV 6 using the intravital dyes fluorescein diacetate and propidium iodide. IGF-I and bFGF reduced ethanol's toxic effect on neuronal survival. Estrogen, bFGF, and NGF increased total neurite length after ethanol treatment. Although none of the treatments had a statistically significant effect on the mean number of primary neurites, all caused a statistically significant increase in the mean number of secondary neurites per cell (a measure of neuritic branching) relative to the ethanol treatment alone.
Barclay
Dawn C
DC
Harvard Medical School, USA.
Hallbergson
Anna F
AF
Montague
Jeremy R
JR
Mudd
Laura M
LM
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects; D004622:Embryo, Mammalian; D004967:Estrogens / Q000494:pharmacology*; D000431:Ethanol / Q000633:toxicity*; D005260:Female; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000517:prevention & control*; D051381:Rats
D004967:Estrogens; D009414:Nerve Growth Factors; D018696:Neuroprotective Agents; D000431:Ethanol