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image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Alcoholism Clinical ...arrow_drop_down
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Alcoholism Clinical and Experimental Research
Article . 2007 . Peer-reviewed
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Temporal Vulnerability of Fetal Cerebellar Purkinje Cells to Chronic Binge Alcohol Exposure: Ovine Model

Authors: Timothy A. Cudd; Wei-Jung A. Chen; Jayanth Ramadoss; James R. West; Emilie R. Lunde;

Temporal Vulnerability of Fetal Cerebellar Purkinje Cells to Chronic Binge Alcohol Exposure: Ovine Model

Abstract

Background:  Human magnetic resonance imaging (MRI) and autopsy studies reveal abnormal cerebellar development in children who had been exposed to alcohol prenatally, independent of the exposure period. Animal studies conducted utilizing the rat model similarly demonstrate a broad period of vulnerability, albeit the third trimester‐equivalent of human brain development is reported to be the most vulnerable period, and the first trimester‐equivalent exposure produces cerebellar Purkinje cell loss only at high doses of alcohol. However, in the rat model, all 3 trimester‐equivalents do not occur prenatally, requiring the assumption that intrauterine environment, placenta, maternal interactions, and parturition do not play an important role in mediating the damage. In this study, we utilized the ovine model, where all 3 trimester‐equivalents occur in utero, to determine the critical window of vulnerability of fetal cerebellar Purkinje cells.Methods:  Four groups of pregnant sheep were used: first trimester‐equivalent pair‐fed saline control group, first trimester‐equivalent alcohol group (1.75 g/kg), third trimester‐equivalent pair‐fed saline control group, and third trimester‐equivalent alcohol group (1.75 g/kg). The alcohol exposure regimen was designed to mimic a human binge pattern. Alcohol was administered intravenously on 3 consecutive days beginning on day 4 and day 109 of gestation in the first and third trimester‐equivalent groups, respectively, and the alcohol treatment was followed by a 4‐day inter‐treatment interval when the animals were not exposed to alcohol. Such treatment episodes were replicated until gestational day 41 and 132 in the first and third trimester‐equivalent groups, respectively. All fetal brains were harvested on day 133 and processed for stereological cerebellar Purkinje cell counting.Results:  Significant deficits were found in the fetal cerebellar Purkinje cell number and density in the first and third trimester‐equivalent alcohol exposed fetuses compared with those in the saline controls. However, there was no difference between the first and third trimester‐equivalent alcohol administered groups. When comparing the present findings to those from a previous study where the duration of alcohol exposure was all 3 trimester‐equivalents of gestation, we did not detect a difference in fetal cerebellar Purkinje cell number.Conclusions:  We conclude that the fetal cerebellar Purkinje cells are sensitive to alcohol exposure at any time during gestation and that women who engage in binge drinking during the first trimester are at a high risk of giving birth to children with cerebellar damage even if drinking ceases after the first trimester. Our findings also support the hypothesis that only a certain population of Purkinje cells are vulnerable to alcohol‐induced depletion irrespective of the timing or duration of alcohol exposure.

Keywords

Sheep, Alcohol Drinking, Ethanol, Central Nervous System Depressants, Cell Count, Alcoholism, Disease Models, Animal, Purkinje Cells, Pregnancy, Cerebellum, Animals, Female, Maternal-Fetal Exchange

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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
37
Top 10%
Top 10%
Top 10%
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