Journal article
Lithium Inhibits GSK3β and Augments GluN2A Receptor Expression in the Prefrontal Cortex
Frontiers in cellular neuroscience, v 12, pp 16-16
01 Feb 2018
PMID: 29449801
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Glycogen synthase kinase 3β (GSK3β) is a highly conserved serine/threonine kinase that has been implicated in both psychiatric and neurodegenerative diseases including schizophrenia, bipolar disorder, and Alzheimer's disease; therefore regulating its activity has become an important strategy for treatment of cognitive impairments in these disorders. This study examines the effects of lithium on GSK3β and its interaction with β-catenin and NMDA receptors within the prefrontal cortex. Lithium, a clinically relevant drug commonly prescribed as a mood stabilizer for psychiatric disorders, significantly increased levels of phosphorylated GSK3β serine 9, an inhibitory phosphorylation site, and decreased β-catenin ser33/37/thr41 phosphorylation
in vitro
, indicating GSK3β inhibition and reduced β-catenin degradation. GluN2A subunit levels were concurrently increased following lithium treatment. Similar alterations were also demonstrated
in vivo;
lithium administration increased GSK3β serine 9 phosphorylation and GluN2A levels, suggesting a reduced GSK3β activity and augmented GluN2A expression. Correspondingly, we observed that the amplitudes of evoked GluN2A-mediated excitatory postsynaptic currents in mPFC pyramidal neurons were significantly increased following lithium administration. Our data suggest that GSK3β activity negatively regulates GluN2A expression, likely by mediating upstream β-catenin phosphorylation, in prefrontal cortical neurons. Furthermore, our biochemical and electrophysiological experiments demonstrate that lithium mediates a specific increase in GluN2A subunit expression, ultimately augmenting GluN2A-mediated currents in the prefrontal cortex.
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Details
- Title
- Lithium Inhibits GSK3β and Augments GluN2A Receptor Expression in the Prefrontal Cortex
- Creators
- Sarah A Monaco - ,Brielle R Ferguson - ,Wen-Jun Gao - ,
- Publication Details
- Frontiers in cellular neuroscience, v 12, pp 16-16
- Publisher
- Frontiers Media S.A
- Grant note
- NIH R01MH085666 / National Institutes of Health
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Neurobiology and Anatomy
- Web of Science ID
- WOS:000423826900001
- Scopus ID
- 2-s2.0-85043515411
- Other Identifier
- 991014877933104721
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- Web of Science research areas
- Neurosciences