Dose-Related Reduction in Hippocampal Neuronal Populations in Fetal Alcohol Exposed Vervet Monkeys

Fetal alcohol spectrum disorder (FASD) is a chronic debilitating condition resulting in behavioral and intellectual impairments and is considered the most prevalent form of preventable mental retardation in the industrialized world. We previously reported that 2-year-old offspring of vervet monkey (...

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Main Authors: Mark W. Burke, Hocine Slimani, Maurice Ptito, Frank R. Ervin, Roberta M. Palmour
Format: Article
Language:English
Published: MDPI AG 2022-08-01
Series:Brain Sciences
Subjects:
Online Access:https://www.mdpi.com/2076-3425/12/9/1117
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author Mark W. Burke
Hocine Slimani
Maurice Ptito
Frank R. Ervin
Roberta M. Palmour
author_facet Mark W. Burke
Hocine Slimani
Maurice Ptito
Frank R. Ervin
Roberta M. Palmour
author_sort Mark W. Burke
collection DOAJ
description Fetal alcohol spectrum disorder (FASD) is a chronic debilitating condition resulting in behavioral and intellectual impairments and is considered the most prevalent form of preventable mental retardation in the industrialized world. We previously reported that 2-year-old offspring of vervet monkey (<i>Chlorocebus sabeus</i>) dams drinking, on average, 2.3 ± 0.49 g ethanol per Kg maternal body weight 4 days per week during the last third of pregnancy had significantly lower numbers of CA1 (−51.6%), CA2 (−51.2%) and CA3 (−42.8%) hippocampal neurons, as compared to age-matched sucrose controls. Fetal alcohol-exposed (FAE) offspring also showed significantly lower volumes for these structures at 2 years of age. In the present study, we examined these same parameters in 12 FAE offspring with a similar average but a larger range of ethanol exposures (1.01–2.98 g/Kg/day; total ethanol exposure 24–158 g/Kg). Design-based stereology was performed on cresyl violet-stained and doublecortin (DCX)-immunostained sections of the hippocampus. We report here significant neuronal deficits in the hippocampus with a significant negative correlation between daily dose and neuronal population in CA1 (<i>r</i><sup>2</sup> = 0.486), CA2 (<i>r</i><sup>2</sup> = 0.492), and CA3 (<i>r</i><sup>2</sup> = 0.469). There were also significant correlations between DCX population in the dentate gyrus and daily dose (<i>r</i><sup>2</sup> = 0.560). Both correlations were consistent with linear dose-response models. This study illustrates that neuroanatomical sequelae of fetal ethanol exposure are dose-responsive and suggests that there may be a threshold for this effect.
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spelling doaj.art-9505d155bb67401d93095faf41ede3782023-11-23T15:19:26ZengMDPI AGBrain Sciences2076-34252022-08-01129111710.3390/brainsci12091117Dose-Related Reduction in Hippocampal Neuronal Populations in Fetal Alcohol Exposed Vervet MonkeysMark W. Burke0Hocine Slimani1Maurice Ptito2Frank R. Ervin3Roberta M. Palmour4Department of Physiology and Biophysics, Howard University, Washington, DC 20059, USASchool of Optometry and Department of Physiology, Université de Montréal, Montréal, QC H3C 3J7, CanadaSchool of Optometry and Department of Physiology, Université de Montréal, Montréal, QC H3C 3J7, CanadaBehavioural Science Foundation, St. Kitts, Saint Kitts and NevisBehavioural Science Foundation, St. Kitts, Saint Kitts and NevisFetal alcohol spectrum disorder (FASD) is a chronic debilitating condition resulting in behavioral and intellectual impairments and is considered the most prevalent form of preventable mental retardation in the industrialized world. We previously reported that 2-year-old offspring of vervet monkey (<i>Chlorocebus sabeus</i>) dams drinking, on average, 2.3 ± 0.49 g ethanol per Kg maternal body weight 4 days per week during the last third of pregnancy had significantly lower numbers of CA1 (−51.6%), CA2 (−51.2%) and CA3 (−42.8%) hippocampal neurons, as compared to age-matched sucrose controls. Fetal alcohol-exposed (FAE) offspring also showed significantly lower volumes for these structures at 2 years of age. In the present study, we examined these same parameters in 12 FAE offspring with a similar average but a larger range of ethanol exposures (1.01–2.98 g/Kg/day; total ethanol exposure 24–158 g/Kg). Design-based stereology was performed on cresyl violet-stained and doublecortin (DCX)-immunostained sections of the hippocampus. We report here significant neuronal deficits in the hippocampus with a significant negative correlation between daily dose and neuronal population in CA1 (<i>r</i><sup>2</sup> = 0.486), CA2 (<i>r</i><sup>2</sup> = 0.492), and CA3 (<i>r</i><sup>2</sup> = 0.469). There were also significant correlations between DCX population in the dentate gyrus and daily dose (<i>r</i><sup>2</sup> = 0.560). Both correlations were consistent with linear dose-response models. This study illustrates that neuroanatomical sequelae of fetal ethanol exposure are dose-responsive and suggests that there may be a threshold for this effect.https://www.mdpi.com/2076-3425/12/9/1117fetal alcohol exposurehippocampusimmature neuronsstereology
spellingShingle Mark W. Burke
Hocine Slimani
Maurice Ptito
Frank R. Ervin
Roberta M. Palmour
Dose-Related Reduction in Hippocampal Neuronal Populations in Fetal Alcohol Exposed Vervet Monkeys
Brain Sciences
fetal alcohol exposure
hippocampus
immature neurons
stereology
title Dose-Related Reduction in Hippocampal Neuronal Populations in Fetal Alcohol Exposed Vervet Monkeys
title_full Dose-Related Reduction in Hippocampal Neuronal Populations in Fetal Alcohol Exposed Vervet Monkeys
title_fullStr Dose-Related Reduction in Hippocampal Neuronal Populations in Fetal Alcohol Exposed Vervet Monkeys
title_full_unstemmed Dose-Related Reduction in Hippocampal Neuronal Populations in Fetal Alcohol Exposed Vervet Monkeys
title_short Dose-Related Reduction in Hippocampal Neuronal Populations in Fetal Alcohol Exposed Vervet Monkeys
title_sort dose related reduction in hippocampal neuronal populations in fetal alcohol exposed vervet monkeys
topic fetal alcohol exposure
hippocampus
immature neurons
stereology
url https://www.mdpi.com/2076-3425/12/9/1117
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AT mauriceptito doserelatedreductioninhippocampalneuronalpopulationsinfetalalcoholexposedvervetmonkeys
AT frankrervin doserelatedreductioninhippocampalneuronalpopulationsinfetalalcoholexposedvervetmonkeys
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