Dataset Information

Phosphodiesterase inhibition increases CREB phosphorylation and restores orientation selectivity in a model of fetal alcohol spectrum disorders.

ABSTRACT:

Background

Fetal alcohol spectrum disorders (FASD) are the leading cause of mental retardation in the western world and children with FASD present altered somatosensory, auditory and visual processing. There is growing evidence that some of these sensory processing problems may be related to altered cortical maps caused by impaired developmental neuronal plasticity.

Methodology/principal findings

Here we show that the primary visual cortex of ferrets exposed to alcohol during the third trimester equivalent of human gestation have decreased CREB phosphorylation and poor orientation selectivity revealed by western blotting, optical imaging of intrinsic signals and single-unit extracellular recording techniques. Treating animals several days after the period of alcohol exposure with a phosphodiesterase type 1 inhibitor (Vinpocetine) increased CREB phosphorylation and restored orientation selectivity columns and neuronal orientation tuning.

Conclusions/significance

These findings suggest that CREB function is important for the maturation of orientation selectivity and that plasticity enhancement by vinpocetine may play a role in the treatment of sensory problems in FASD.

SUBMITTER: Krahe TE

PROVIDER: S-EPMC2721629 | biostudies-literature | 2009 Aug

REPOSITORIES: biostudies-literature

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Publications

Phosphodiesterase inhibition increases CREB phosphorylation and restores orientation selectivity in a model of fetal alcohol spectrum disorders.

Krahe Thomas E TE Wang Weili W Medina Alexandre E AE

PloS one 20090814 8

<h4>Background</h4>Fetal alcohol spectrum disorders (FASD) are the leading cause of mental retardation in the western world and children with FASD present altered somatosensory, auditory and visual processing. There is growing evidence that some of these sensory processing problems may be related to altered cortical maps caused by impaired developmental neuronal plasticity.<h4>Methodology/principal findings</h4>Here we show that the primary visual cortex of ferrets exposed to alcohol during the ...[more]

PMID: 19680548

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Project description:The pathology of fetal alcohol syndrome and the less severe fetal alcohol spectrum disorders includes brain dysmyelination. Recent studies have shed light on the molecular mechanisms underlying these white matter abnormalities. Rodent models of fetal alcohol syndrome and human studies have shown suppressed oligodendrocyte differentiation and apoptosis of oligodendrocyte precursor cells. Ethanol exposure led to reduced expression of myelin basic protein and delayed myelin basic protein expression in rat and mouse models of fetal alcohol syndrome and in human histopathological specimens. Several studies have reported increased expression of many chemokines in dysmyelinating disorders in central nervous system, including multiple sclerosis and fetal alcohol syndrome. Acute ethanol exposure reduced levels of the neuroprotective insulin-like growth factor-1 in fetal and maternal sheep and in human fetal brain tissues, while ethanol increased the expression of tumor necrosis factor α in mouse and human neurons. White matter lesions have been induced in the developing sheep brain by alcohol exposure in early gestation. Rat fetal alcohol syndrome models have shown reduced axon diameters, with thinner myelin sheaths, as well as reduced numbers of oligodendrocytes, which were also morphologically aberrant oligodendrocytes. Expressions of markers for mature myelination, including myelin basic protein, also were reduced. The accumulating knowledge concerning the mechanisms of ethanol-induced dysmyelination could lead to the development of strategies to prevent dysmyelination in children exposed to ethanol during fetal development. Future studies using fetal oligodendrocyte- and oligodendrocyte precursor cell-derived exosomes isolated from the mother's blood may identify biomarkers for fetal alcohol syndrome and even implicate epigenetic changes in early development that affect oligodendrocyte precursor cell and oligodendrocyte function in adulthood. By combining various imaging modalities with molecular studies, it may be possible to determine which fetuses are at risk and to intervene therapeutically early in the pregnancy.

Dataset Information

Phosphodiesterase inhibition increases CREB phosphorylation and restores orientation selectivity in a model of fetal alcohol spectrum disorders.

Background

Methodology/principal findings

Conclusions/significance

Publications

Phosphodiesterase inhibition increases CREB phosphorylation and restores orientation selectivity in a model of fetal alcohol spectrum disorders.

Similar Datasets

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