TY - JOUR

T1 - Dose-Related Reduction in Hippocampal Neuronal Populations in Fetal Alcohol Exposed Vervet Monkeys

AU - Burke, Mark W.

AU - Slimani, Hocine

AU - Ptito, Maurice

AU - Ervin, Frank R.

AU - Palmour, Roberta M.

PY - 2022

Y1 - 2022

N2 - 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 (Chlorocebus sabeus) 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 (r(2) = 0.486), CA2 (r(2) = 0.492), and CA3 (r(2) = 0.469). There were also significant correlations between DCX population in the dentate gyrus and daily dose (r(2) = 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.

AB - 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 (Chlorocebus sabeus) 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 (r(2) = 0.486), CA2 (r(2) = 0.492), and CA3 (r(2) = 0.469). There were also significant correlations between DCX population in the dentate gyrus and daily dose (r(2) = 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.

KW - fetal alcohol exposure

KW - hippocampus

KW - immature neurons

KW - stereology

KW - PRENATAL ETHANOL EXPOSURE

KW - SYNAPTIC PLASTICITY

KW - SPECTRUM DISORDERS

KW - DENTATE GYRUS

KW - GRANULE CELLS

KW - BEHAVIOR

KW - CONSUMPTION

KW - PREVALENCE

KW - PREGNANCY

KW - CHILDREN

U2 - 10.3390/brainsci12091117

DO - 10.3390/brainsci12091117

M3 - Journal article

C2 - 36138853

VL - 12

JO - Brain Sciences

JF - Brain Sciences

SN - 2076-3425

IS - 9

M1 - 1117

ER -