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
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.
| Tang, Shiyu; Xu, Su; Gullapalli, Rao P et al. (2018) Effects of Early Alcohol Exposure on Functional Organization and Microstructure of a Visual-Tactile Integrative Circuit. Alcohol Clin Exp Res 42:727-734 |
| Pulimood, Nisha S; Rodrigues Junior, Wandilson Dos Santos; Atkinson, Devon A et al. (2017) The Role of CREB, SRF, and MEF2 in Activity-Dependent Neuronal Plasticity in the Visual Cortex. J Neurosci 37:6628-6637 |
| Sours, Chandler; Raghavan, Prashant; Foxworthy, W Alex et al. (2017) Cortical multisensory connectivity is present near birth in humans. Brain Imaging Behav 11:1207-1213 |
| Krahe, Thomas E; Filgueiras, Claudio C; Medina, Alexandre E (2016) Effects of developmental alcohol and valproic acid exposure on play behavior of ferrets. Int J Dev Neurosci 52:75-81 |
| 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 NRX1? and NL1 via Hevin. Cell 164:183-196 |
| 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 |
| 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 |
| 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 |
| 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 |
Showing the most recent 10 out of 20 publications
