| First Author | Banach E | Year | 2022 |
| Journal | Neuroscience | Volume | 490 |
| Pages | 287-295 | PubMed ID | 35331845 |
| Mgi Jnum | J:347006 | Mgi Id | MGI:7278633 |
| Doi | 10.1016/j.neuroscience.2022.03.024 | Citation | Banach E, et al. (2022) Dysregulation of miRNAs Levels in Glycogen Synthase Kinase-3beta Overexpressing Mice and the Role of miR-221-5p in Synaptic Function. Neuroscience 490:287-295 |
| abstractText | Glycogen synthase kinase-3beta (GSK-3beta) is a highly expressed kinase in the brain, where it has an important role in synaptic plasticity. Aberrant activity of GSK-3beta leads to synaptic dysfunction which results in the development of several neuropsychiatric and neurological diseases. Notably, overexpression of constitutively active form of GSK-3beta (GSK-3beta[S9A]) in mice recapitulates the cognitive and structural defects characteristic for neurological and psychiatric disorders. However, the mechanisms by which GSK-3beta regulates synaptic functions are not clearly known. Here, we investigate the effects of GSK-3beta overactivity on neuronal miRNA expression in the mouse hippocampus. We found that GSK-3beta overactivity downregulates miRNA network with a potent effect on miR-221-5p (miR-221*). Next, characterization of miR-221* function in primary hippocampal cell culture transfected by miR-221* inhibitor, showed no structural changes in dendritic spine shape and density. Using electrophysiological methods, we found that downregulation of miR-221* increases excitatory synaptic transmission in hippocampal neurons, probably via postsynaptic mechanisms. Thus, our data reveal potential mechanism by which GSK-3beta and miRNAs might regulate synaptic function and therefore also synaptic plasticity. |
