Dr. George Henderson - Faculty Page

                           

Alcohol, Environmental Toxins, Neurons, Apoptosis, Oxidative Stress, Nanoparticle Drug Delivery 

The primary objective of my research is to gain a better understanding of the basic mechanisms underlying alcohol and oxidative stress-induced damage to the developing brain and placenta. We utilize an animal model for Fetal Alcohol Spectrum Disorder, the major cause of preventable birth defects for which there is no therapeutic intervention. The pro-oxidant effects of ethanol have been documented in adult and fetal tissues (brain, placenta, and liver) using in vivo rat models and in primary cultures of fetal rat cortical neurons and neonatal rat cortical astrocytes. Prior studies focused on the accelerated apoptotic death of neurons exposed to alcohol with mitochondria as the source of reactive oxygen species and astrocyte-mediated protection from this apoptotic death. 

Findings in our laboratory have illustrated that the well- documented increase in fetal neuron death in the ethanol-exposed developing brain is due to enhanced mitochondrially-mediated apoptotic cell death (intrinsic signaling pathways). Confocal and multiphoton imaging of live fetal cortical neurons illustrated that ethanol can elicit an increase in reactive oxygen species within only minutes of exposure and that this is associated with decreased levels of the antioxidant, glutathione. This occurs in placenta as well, thus the fetus is also deprived of placental growth support and protection against this oxidative stress-induced apoptotic death by maintaining neuron glutathione homeostasis. With these understandings of the specific biochemical pathways damaged by ethanol, we can now use this information to develop specific targets of intervention/rescue. 

Current studies are developing potential therapeutic interventions to the fetotoxic effects of ethanol employing a new nanoparticle-mediated drug delivery specifically to placental cells. These treatments are designed to optimize placental support of compromised fetal brain development while avoiding off-target adverse effects that would occur with fetal brain exposure to medications. This lipid nanocarrier system has strong therapeutic potential and can be applied to other clinical settings of placenta dysfunction.