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Prenatal Alcohol Exposure Leads to Enhanced Serine 9 Phosphorylation of Glycogen Synthase Kinase‐3 β (GSK‐3 β ) in the Hippocampal Dentate Gyrus of Adult Mouse
Author(s) -
Cunningham Lee Anna,
Newville Jessie,
Li Lu,
Tapia Phillip,
Allan Andrea M.,
Valenzuela C. Fernando
Publication year - 2017
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/acer.13489
Subject(s) - dentate gyrus , hippocampal formation , gsk 3 , gsk3b , glycogen synthase , gabaergic , phosphorylation , neuroscience , biology , kinase , neurogenesis , microbiology and biotechnology , chemistry , endocrinology , medicine , inhibitory postsynaptic potential
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 GABA ergic 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, GABA ergic interneurons, and CA primary neurons as major targets of this dysregulation.