Abstract

Alcohol consumption during pregnancy can lead to a multitude of neurological problems in offspring, varying from subtle behavioral changes to severe mental retardation. These alterations are collectively referred to as Fetal Alcohol Spectrum Disorders (FASD). Early alcohol exposure can strongly affect the visual system and children with FASD can exhibit an amblyopia-like pattern of visual acuity deficits even in the absence of optical and oculomotor disruption. Here, we test whether early alcohol exposure can lead to a disruption in visual acuity, using a model of FASD to mimic alcohol consumption in the last months of human gestation. To accomplish this, mice were exposed to ethanol (5 g/kg i.p.) or saline on postnatal days (P) 5, 7, and 9. Two to three weeks later we recorded visually evoked potentials to assess spatial frequency detection and contrast sensitivity, conducted electroretinography (ERG) to further assess visual function and imaged retinotopy using optical imaging of intrinsic signals. We observed that animals exposed to ethanol displayed spatial frequency acuity curves similar to controls. However, ethanol-treated animals showed a significant deficit in contrast sensitivity. Moreover, ERGs revealed a market decrease in both a- and b-waves amplitudes, and optical imaging suggest that both elevation and azimuth maps in ethanol-treated animals have a 10–20° greater map tilt compared to saline-treated controls. Overall, our findings suggest that binge alcohol drinking restricted to the last months of gestation in humans can lead to marked deficits in visual function.

Highlights

  • Fetal Alcohol Spectrum Disorder (FASD) is an umbrella term for a variety of conditions affecting the children of women who drink alcohol during pregnancy and is currently one of the leading causes of mental retardation in the world

  • visually evoked potentials (VEPs) AMPLITUDES At P25, contralateral bias was assessed by peak to trough measures of VEPs resulting from stimulation of each eye individually

  • (C) Representative VEPs from an ethanol and a saline-treated animal after visual stimulation at different contrasts. (C,D) As contrast decreases, saline-treated animals have a slow decrease in responses, showing a small response to 5% contrast, while ethanol-treated animals sharply drop-off their responses after 100% contrast, with no response occurring at 10% contrast

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Summary

Introduction

Fetal Alcohol Spectrum Disorder (FASD) is an umbrella term for a variety of conditions affecting the children of women who drink alcohol during pregnancy and is currently one of the leading causes of mental retardation in the world. A subgroup of FASD is Fetal Alcohol Syndrome (FAS), which is characterized by the triad of growth deficiency, central nervous system (CNS) problems, and a specific pattern of facial dysmorphology [3,4,5]. The altered facial features, which include small (or lack of) philtrum, short nose, flat midface, and low nasal bridge are caused by a specific effect of alcohol during the gastrulation phase of development [6,7,8]. The type of visual deficit observed is strongly related to the time of alcohol exposure. Similar to the typical FAS facial dysmorphology, gross ocular defects such as microphthalmia and hypoplasia of the optic nerve are caused by alcohol exposure during the first trimester of the human gestation [6, 8, 14]

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