Office: 210-567-4875
Email: hendersong@uthscsa.edu

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. The pro-oxidant effects of ethanol have been documented in adult and fetal tissues (brain and liver) using in vivo models and in primary cultures of fetal rat cortical neurons and neonatal rat cortical astrocytes. Current studies are focusing 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 neuron death in the ethanol-exposed developing brain may be due to enhanced mitochondrially-mediated apoptosis (intrinsic pathways). Confocal and multiphoton imaging of live fetal cortical neurons have 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. New findings illustrate that astrocytes provide protection against this oxidative stress-induced apoptotic death by maintaining neuron glutathione homeostasis. The system that provides this neuroprotection can be up-regulated at, at least four points, each of which is mediated by an "antioxidant response element"(ARE). This transcriptional-level regulation can be manipulated and studies are ongoing to adapt this to controlled neuroprotection.

In summary, current studies address oxidative stress-mediated apoptotic neuron death in the developing brain, the role of glutathione antioxidant systems in protection against this, and the glia-mediated neuroprotection.

Selected Publications

Rathinam ML, Watts LT, Stark AA, Mahimaimathan L, Stewart J, Schenker S, Henderson GI. Astrocyte control of fetal cortical neuron glutathione homeostasis: Up-regulation by ethanol. J. Neurochem. 96: 1289-1300, 2006.

Watts LT, Rathinam ML, Schenker S, Henderson GI. Astrocytes protect neurons from ethanol-induced oxidative stress and apoptotic death. J Neurosci Res. 80:655-666, 2005.

Ramachandran V, Watt LT, Maffi S, Chen JJ, Schenker S, Henderson GI. Ethanol-Induced Oxidative Stress Precedes Mitochondrially-Mediated Apoptotic Death of Cultured Fetal Cortical Neurons. J Neuroscience Research V74:577-588, 2003.

Musatov A, Carroll C, Liu YC, Henderson G, Weintraub S, Robinson N. Identification of Bovine Heart Cytochrome c Oxidase Subunits Modified by the Lipid Peroxidation Product 4-Hydroxy-2-Nonenal. Biochemistry 41:8212-8220, 2002.

Ramachandran V, Perez A, Chen JJ, Senthil D, Schenker S, Henderson GI. In Utero Ethanol Exposure Caused Mitochondrial Dysfunction Which Can Result in Apoptotic Cell Death In Fetal Brain: A Potential Role for 4-Hydroxynonenal. Alcohol Clin Exp Res 25: 862-872, 2001.