Prenatal Alcohol Exposure Leads to Enhanced Serine 9 Phosphorylation of Glycogen Synthase Kinase‐3β (GSK‐3β) in the Hippocampal Dentate Gyrus of Adult Mouse. (3rd October 2017)

• Record Type: Journal Article
• Authors: Cunningham, Lee Anna; Newville, Jessie; Li, Lu; Tapia, Phillip; Allan, Andrea M.; Valenzuela, C. Fernando
• Is Part Of: Alcoholism. Volume 41:Number 11(2017)
• Page Start: 1907
• Page End: 1916
• Publication Date: 2017-10-03
• Subjects: Fetal Alcohol Spectrum Disorders -- Glycogen Synthase Kinase -- Hippocampal Neurogenesis -- Hippocampal Plasticity -- Hilar Mossy Cells; Alcoholism -- Periodicals; Alcoholism -- Periodicals; Alcoolisme; Electronic journals; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.861005
• DOI: 10.1111/acer.13489
• Languages: English
• ISSNs: 0145-6008

Abstract

Abstract : Background: The goal of this study was to evaluate the expression and serine 9 phosphorylation of glycogen synthase kinase (GSK‐3 β ) within the adult hippocampal dentate gyrus (DG) in a preclinical mouse model of fetal alcohol spectrum disorders. GSK‐3 β is a multifunctional kinase that modulates many hippocampal processes affected by gestational alcohol, including synaptic plasticity and adult neurogenesis. GSK‐3 β is a constitutively active kinase that is negatively regulated by phosphorylation at the serine 9 residue. Methods: We utilized a well‐characterized limited access "drinking‐in‐the‐dark" paradigm of prenatal alcohol exposure (PAE) and measured p(Ser9)GSK‐3 β and total GSK‐3 β within adult DG by Western blot analysis. In addition, we evaluated the expression pattern of both p(Ser9)GSK‐3 β and total GSK‐3 β within the adult hippocampal dentate of PAE and control mice using high‐resolution confocal microscopy. Results: Our findings demonstrate a marked 2.0‐fold elevation of p(Ser9)GSK‐3 β in PAE mice, concomitant with a more moderate 36% increase in total GSK‐3 β . This resulted in an approximate 63% increase in the p(Ser9)GSK‐3 β /GSK‐3 β ratio. Immunostaining revealed robust GSK‐3 β expression within Cornu Ammonis (CA) pyramidal neurons, hilar mossy cells, and a subset of GABAergic interneurons, with low levels of expression within hippocampal progenitors and dentate granule cells. Conclusions: These findings suggest that PAE may lead to a long‐term disruption of GSK‐3 β signaling within the DG, and implicate mossy cells, GABAergic interneurons, and CA primary neurons as major targets of this dysregulation. Abstract : GSK‐3 β is a multifunctional kinase that modulates many hippocampal processes affected by gestational alcohol. Using a limited access prenatal alcohol exposure (PAE) paradigm, we evaluated the expression of p(Ser9)GSK‐3 β and total GSK‐3 β within the adult hippocampal dentate of PAE and control mice using western blot analysis and high resolution confocal microscopy. Our results demonstrate elevated levels of p(Ser9)GSK‐3 β (inactive form) in PAE mice, and implicate mossy cells, GABAergic interneurons, and CA pyramidal neurons as potential sources of PAE‐induced GSK‐3 β dysregulation.