Fetal Alcohol Spectrum Disorders (FASD) is an umbrella term describing a range of effects that can occur in an individual whose mother imbibed alcohol during pregnancy. This condition is considered the leading cause of mental retardation in the western world with as many as 40,000 cases per year in the United States. The sensory cortex is one of the most affected areas in FASD and children with this condition present altered somatosensory, auditory and visual processing. There is growing evidence indicating that these sensory problems may be related to poor cortical map refinement, organization and plasticity. However, the mechanisms that underlie such effects remain to be elucidated. We developed a unique ferret model of FASD that provides a novel approach to test mechanistic hypothesis of how early alcohol exposure can impair sensory cortex function. We showed that third trimester alcohol exposure lead to a persistent disruption in visual cortex organization and neuronal plasticity. In recent years, much attention has been devoted to the control of neuronal function by astrocytes. It has been shown that molecules secreted by astrocytes can regulate synaptic formation, stabilization and plasticity. Many of these astrocyte-released molecules are mediated by the transcription factor SRF (Serum Response Factor). Here we hypothesize that inappropriate SRF function in astrocytes contributes to the impairment of neuronal plasticity seen in FASD. As a corollary, improvement of SRF function in astrocytes may ameliorate this deficit. To test this hypothesis we will use multiple techniques such as viral-mediated gene transfer, ex vivo gene delivery, in vivo optical imaging of intrinsic signals, in vivo extracellular electrophysiology, monotypic cell cultures, confocal laser microscopy and multiple biochemical and molecular assays. Collectively, this proposal will help our understanding of how early alcohol exposure affects astrocyte to neuron signaling and its effects on cortical plasticity. This information may be highly relevant to devise therapeutic interventions for FASD

Public Health Relevance

Fetal alcohol spectrum disorder (FASD) is a leading cause of mental retardation. Here we test the hypothesis that impairment of astrocytes function can impact plasticity in neurons. As corollary, improvement of astrocytes function can lead to an increase in neuronal plasticity. These studies should contribute to devise therapeutic interventions that may alleviate morbidity in FASD.

National Institute of Health (NIH)
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
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Neurotoxicology and Alcohol Study Section (NAL)
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Hereld, Dale
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University of Maryland Baltimore
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Trindade, Pablo; Hampton, Brian; Manhães, Alex C et al. (2016) Developmental alcohol exposure leads to a persistent change on astrocyte secretome. J Neurochem 137:730-43
Singh, Sandeep K; Stogsdill, Jeff A; Pulimood, Nisha S et al. (2016) Astrocytes Assemble Thalamocortical Synapses by Bridging NRX1α and NL1 via Hevin. Cell 164:183-96
Krahe, Thomas E; Medina, Alexandre E; Lantz, Crystal L et al. (2015) Hyperactivity and depression-like traits in Bax KO mice. Brain Res 1625:246-54
Lantz, Crystal L; Sipe, Grayson O; Wong, Elissa L et al. (2015) Effects of Developmental Alcohol Exposure on Potentiation and Depression of Visual Cortex Responses. Alcohol Clin Exp Res 39:1434-42
Foxworthy, W Alex; Medina, Alexandre E (2015) Overexpression of Serum Response Factor in Neurons Restores Ocular Dominance Plasticity in a Model of Fetal Alcohol Spectrum Disorders. Alcohol Clin Exp Res 39:1951-6
Filgueiras, Claudio C; Pohl-Guimaraes, Fernanda; Krahe, Thomas E et al. (2013) Sodium valproate exposure during the brain growth spurt transiently impairs spatial learning in prepubertal rats. Pharmacol Biochem Behav 103:684-91
Lantz, Crystal L; Wang, Weili; Medina, Alexandre E (2012) Early alcohol exposure disrupts visual cortex plasticity in mice. Int J Dev Neurosci 30:351-7
Paul, A P; Medina, A E (2012) Overexpression of serum response factor in astrocytes improves neuronal plasticity in a model of early alcohol exposure. Neuroscience 221:193-202
Medina, Alexandre E (2011) Fetal alcohol spectrum disorders and abnormal neuronal plasticity. Neuroscientist 17:274-87
Paul, Arco P; Pohl-Guimaraes, Fernanda; Krahe, Thomas E et al. (2010) Overexpression of serum response factor restores ocular dominance plasticity in a model of fetal alcohol spectrum disorders. J Neurosci 30:2513-20

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