University of Kentucky

A Novel Approach to Study Fetal Alcohol Syndrome: A 3-Trimester Model

Institution

University of Kentucky

Abstract

Estimates from the CDC suggest that the incidence of Fetal Alcohol Spectrum Disorders (FASD’s) can be as high as 2 - 5 per 100 school children. One of the most frequently reported behavioral effects with FASD is ADHD (attention deficit hyperactivity disorder) with estimates as high as 50 – 90% of children with heavy prenatal ethanol (ETOH) exposure having ADHD. Rodent models have been very useful in studying the behavior, neuroanatomy, mechanisms and possible interventions following prenatal ETOH exposure. Until recently, the majority of rodent models have used either a prenatal exposure model (which in terms of brain development is equivalent to the first and 2nd trimester of human pregnancy) or a neonatal exposure model (which overlaps the human third trimester “brain growth spurt”). However, in clinical populations, ETOH consumption may continue throughout the pregnancy and so this project was designed to assess a mouse model of ETOH consumption that included all three trimesters. Female C57Bl/6J mice voluntarily were given ETOH to drink daily prior to and throughout pregnancy (1st and 2nd trimester exposure) and after birth, a subset of pups also received ETOH (3rd trimester exposure). Appropriate controls were included. Offspring were tested for hyperactivity prior to adolescence for 30 min on two consecutive days. Offspring exposed to ETOH pre and postnatally (i.e. all 3 trimesters) were hyperactive relative to controls. Those exposed only neonatally were also hyperactive. These data provide support for the sensitivity of the CNS to ETOH during the “3rd trimester brain growth spurt”.

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A Novel Approach to Study Fetal Alcohol Syndrome: A 3-Trimester Model

Estimates from the CDC suggest that the incidence of Fetal Alcohol Spectrum Disorders (FASD’s) can be as high as 2 - 5 per 100 school children. One of the most frequently reported behavioral effects with FASD is ADHD (attention deficit hyperactivity disorder) with estimates as high as 50 – 90% of children with heavy prenatal ethanol (ETOH) exposure having ADHD. Rodent models have been very useful in studying the behavior, neuroanatomy, mechanisms and possible interventions following prenatal ETOH exposure. Until recently, the majority of rodent models have used either a prenatal exposure model (which in terms of brain development is equivalent to the first and 2nd trimester of human pregnancy) or a neonatal exposure model (which overlaps the human third trimester “brain growth spurt”). However, in clinical populations, ETOH consumption may continue throughout the pregnancy and so this project was designed to assess a mouse model of ETOH consumption that included all three trimesters. Female C57Bl/6J mice voluntarily were given ETOH to drink daily prior to and throughout pregnancy (1st and 2nd trimester exposure) and after birth, a subset of pups also received ETOH (3rd trimester exposure). Appropriate controls were included. Offspring were tested for hyperactivity prior to adolescence for 30 min on two consecutive days. Offspring exposed to ETOH pre and postnatally (i.e. all 3 trimesters) were hyperactive relative to controls. Those exposed only neonatally were also hyperactive. These data provide support for the sensitivity of the CNS to ETOH during the “3rd trimester brain growth spurt”.