• Ewa Banach, Aleksandra Szczepankiewicz, Leszek Kaczmarek, Tomasz Jaworski, and Joanna Urban-Ciećko.
• Laboratory of Electrophysiology, Nencki Institute of Experimental Biology, PAS, Warsaw, Poland; Laboratory of Animal Models, Nencki Institute of Experimental Biology, PAS, Warsaw, Poland; Laboratory of Neurobiology, BRAINCITY, Nencki Institute of Experimental Biology, Polish Academy of Sciences, 3 Pasteur Street, 02-093 Warsaw, Poland. Electronic address: ewabanach01@gmail.com.
• Neuroscience. 2022 May 10; 490: 287-295.

AbstractGlycogen synthase kinase-3β (GSK-3β) is a highly expressed kinase in the brain, where it has an important role in synaptic plasticity. Aberrant activity of GSK-3β leads to synaptic dysfunction which results in the development of several neuropsychiatric and neurological diseases. Notably, overexpression of constitutively active form of GSK-3β (GSK-3β[S9A]) in mice recapitulates the cognitive and structural defects characteristic for neurological and psychiatric disorders. However, the mechanisms by which GSK-3β regulates synaptic functions are not clearly known. Here, we investigate the effects of GSK-3β overactivity on neuronal miRNA expression in the mouse hippocampus. We found that GSK-3β 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-3β and miRNAs might regulate synaptic function and therefore also synaptic plasticity.Copyright © 2022 IBRO. Published by Elsevier Ltd. All rights reserved.

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