| First Author | Cunningham LA | Year | 2017 |
| Journal | Alcohol Clin Exp Res | Volume | 41 |
| Issue | 11 | Pages | 1907-1916 |
| PubMed ID | 28865114 | Mgi Jnum | J:268820 |
| Mgi Id | MGI:6272569 | Doi | 10.1111/acer.13489 |
| Citation | Cunningham LA, et al. (2017) Prenatal Alcohol Exposure Leads to Enhanced Serine 9 Phosphorylation of Glycogen Synthase Kinase-3beta (GSK-3beta) in the Hippocampal Dentate Gyrus of Adult Mouse. Alcohol Clin Exp Res 41(11):1907-1916 |
| abstractText | BACKGROUND: The goal of this study was to evaluate the expression and serine 9 phosphorylation of glycogen synthase kinase (GSK-3beta) within the adult hippocampal dentate gyrus (DG) in a preclinical mouse model of fetal alcohol spectrum disorders. GSK-3beta is a multifunctional kinase that modulates many hippocampal processes affected by gestational alcohol, including synaptic plasticity and adult neurogenesis. GSK-3beta 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-3beta and total GSK-3beta within adult DG by Western blot analysis. In addition, we evaluated the expression pattern of both p(Ser9)GSK-3beta and total GSK-3beta 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-3beta in PAE mice, concomitant with a more moderate 36% increase in total GSK-3beta. This resulted in an approximate 63% increase in the p(Ser9)GSK-3beta/GSK-3beta ratio. Immunostaining revealed robust GSK-3beta 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-3beta signaling within the DG, and implicate mossy cells, GABAergic interneurons, and CA primary neurons as major targets of this dysregulation. |
