• Fetal Alcohol;
  • Neuronal Apoptosis;
  • Microglia;
  • Oxidative Stress;
  • Hypothalamus


Animals exposed to alcohol during the developmental period develop many physiological and behavioral problems because of neuronal loss in various brain areas including the hypothalamus. Because alcohol exposure is known to induce oxidative stress in developing neurons, we tested whether hypothalamic cells from the fetal brain exposed to ethanol (EtOH) may alter the cell–cell communication between neurons and microglia, thereby leading to increased oxidative stress and the activation of apoptotic processes in the neuronal population in the hypothalamus.


Using enriched neuronal and microglial cells from fetal rat hypothalami, we measured cellular levels of various oxidants (inline image, reactive oxygen species, nitrite), antioxidants (glutathione [GSH]), antioxidative enzymes (glutathione peroxidase [GSH-Px], catalase, superoxide dismutase) and apoptotic death in neurons in the presence and absence of EtOH or EtOH-treated microglial culture medium. Additionally, we tested the effectiveness of antioxidative agents in preventing EtOH or EtOH-treated microglial conditioned medium actions on oxidative stress and apoptosis in neuronal cell cultures.


Neuronal cell cultures showed increased oxidative stress, as demonstrated by higher cellular levels of oxidants but lower levels of antioxidant and antioxidative enzymes, as well as, increased apoptotic death following treatment with EtOH. These effects of EtOH on oxidative stress and cell death were enhanced by the presence of microglia. Antioxidative agents protected developing hypothalamic neurons from oxidative stress and cellular apoptosis which is caused by EtOH or EtOH-treated microglial culture medium.


These data suggest that exposure of developing hypothalamic neurons to EtOH increases cellular apoptosis via the effects on oxidative stress of neurons directly and via increasing production of microglial-derived factor(s).