title: Prenatal alcohol exposure alters p35, CDK5 and GSK3β in the medial frontal cortex and hippocampus of adolescent mice.
abstract: Fetal alcohol spectrum disorders (FASDs) are the number one cause of preventable mental retardation. An estimated 2-5% of children are diagnosed as having a FASD. While it is known that children prenatally exposed to alcohol experience cognitive deficits and a higher incidence of psychiatric illness later in life, the pathways underlying these abnormalities remain uncertain. GSK3β and CDK5 are protein kinases that are converging points for a vast number of signaling cascades, including those controlling cellular processes critical to learning and memory. We investigated whether levels of GSK3β and CDK5 are affected by moderate prenatal alcohol exposure (PAE), specifically in the hippocampus and medial frontal cortex of the adolescent mouse. In the present work we utilized immunoblotting techniques to demonstrate that moderate PAE increased hippocampal p35 and β-catenin, and decreased total levels of GSK3β, while increasing GSK3β Ser9 and Tyr216 phosphorylation. Interestingly, different alterations were seen in the medial frontal cortex where p35 and CDK5 were decreased and increased total GSK3β was accompanied by reduced Tyr216 of the enzyme. These results suggest that kinase dysregulation during adolescence might be an important contributing factor to the effects of PAE on hippocampal and medial frontal cortical functioning; and by extension, that global modulation of these kinases may produce differing effects depending on brain region.
authors.affiliation: Department of Neuroscience, University of New Mexico School of Medicine, Albuquerque, NM 87131, United States.
authors.forename: Samantha L
authors.initials: SL
authors.lastname: Goggin
authors.affiliation: Department of Neuroscience, University of New Mexico School of Medicine, Albuquerque, NM 87131, United States.
authors.forename: Kevin K
authors.initials: KK
authors.lastname: Caldwell
authors.affiliation: Department of Neuroscience, University of New Mexico School of Medicine, Albuquerque, NM 87131, United States.
authors.forename: Lee Anna
authors.initials: LA
authors.lastname: Cunningham
authors.affiliation: Department of Neuroscience, University of New Mexico School of Medicine, Albuquerque, NM 87131, United States.
authors.forename: Andrea M
authors.initials: AM
authors.lastname: Allan
keywords: CDK5; GSK3β; frontal cortex; hippocampus; prenatal alcohol