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Office: 803 253-5851
Fax: 803 733 1515
E-mail:
USSINGH
@gw.med.sc.edu
Department of Pathology, Microbiology
and Immunology, University of South Carolina School of Medicine, Columbia, SC
29208
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Understanding the retinoic acid (RA) signaling in health and disease is our long
term objective. How a defective retinoic acid signaling leads to fetal alcohol
syndrome in children of alcoholic mothers, and causes neuronal malformations in
maternal diabetes is the focus of our present research work.
Mechanism of Alcohol Induced Neurotoxicity: Excessive intake of alcohol not only
affects normal functioning of the adult brain, but also affects embryonic
development in pregnant women. It increases ethanol level in the blood producing
irreversible neurotoxic effects in the unborn babies that lead to fetal alcohol
syndrome (FAS). Children born with FAS have abnormal facial features with mild
to severe mental retardation. Findings from in vivo studies in experimental
animals have shown that the cerebellum is one of the most sensitive areas in the
brain that is affected by ethanol neurotoxicity. Cerebellar granular neurons (CGNs)
exposed to ethanol lose their potential to undergo proper neuronal
differentiation and eventually undergo apoptosis. RA is locally synthesized in
brain and required for brain patterning during embryonic development. Studies
have shown that ethanol increases RA level in
cerebellum. To study the mechanism of ethanol induced toxicity, and whether RA
is involved, is the focus of our studies.
Neuronal Development in Diabetic Embryopathy: Diabetes mellitus is a common
metabolic disorder that affects the peripheral as well as the central nervous
system (CNS). It increases the risk of dementia by
approximately 60% in elderly population which is associated with cognitive
deficits and neurophysiological and structural changes in the brain. These
changes are due to impairments in differentiation and/or survival of neurons. In
case of maternal diabetes situation becomes more complicated. Children born to
diabetic mothers have high risk of brain developmental disorders. It has been
reported that RA is required for differentiation of neurons in the developing
brain, and maintenance of plasticity and regeneration in the adult neurons. Our
studies have shown that under diabetic condition (hyperglycemia), RA-induced
differentiation of embryonic cortical neurons is impaired. Using rodent animal
model of diabetic embryopathy we are interested in dissecting the RA signaling
components that might be specifically targeted and involved in mediating harmful
effects of diabetes on differentiation of cortical neurons.
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