The GSK-3 Inhibitor CT99021 Enhances the Acquisition of Spatial Learning and the Accuracy of Spatial Memory.

Autor:	Lee Y; Department of Brain and Cognitive Sciences, College of Natural Sciences, Seoul National University, Seoul, South Korea.; Centre for Synaptic Plasticity, School of Physiology, Pharmacology and Neuroscience, University of Bristol, Bristol, United Kingdom.; Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada., Bortolotto ZA; Centre for Synaptic Plasticity, School of Physiology, Pharmacology and Neuroscience, University of Bristol, Bristol, United Kingdom., Bradley CA; Department of Brain and Cognitive Sciences, College of Natural Sciences, Seoul National University, Seoul, South Korea.; Neurosciences and Mental Health, The Hospital for Sick Children, Toronto, ON, Canada.; Genes and Genome Biology, The Hospital for Sick Children, Toronto, ON, Canada., Sanderson TM; Department of Brain and Cognitive Sciences, College of Natural Sciences, Seoul National University, Seoul, South Korea.; Centre for Synaptic Plasticity, School of Physiology, Pharmacology and Neuroscience, University of Bristol, Bristol, United Kingdom.; Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada., Zhuo M; Department of Brain and Cognitive Sciences, College of Natural Sciences, Seoul National University, Seoul, South Korea.; Department of Physiology, University of Toronto, Toronto, ON, Canada., Kaang BK; Department of Brain and Cognitive Sciences, College of Natural Sciences, Seoul National University, Seoul, South Korea.; Department of Biological Sciences, College of Natural Sciences, Seoul National University, Seoul, South Korea., Collingridge GL; Department of Brain and Cognitive Sciences, College of Natural Sciences, Seoul National University, Seoul, South Korea.; Centre for Synaptic Plasticity, School of Physiology, Pharmacology and Neuroscience, University of Bristol, Bristol, United Kingdom.; Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada.; Department of Physiology, University of Toronto, Toronto, ON, Canada.; Tanz Centre for Research in Neurodegenerative Diseases, Toronto, ON, Canada.
Jazyk:	angličtina
Zdroj:	Frontiers in molecular neuroscience [Front Mol Neurosci] 2022 Jan 27; Vol. 14, pp. 804130. Date of Electronic Publication: 2022 Jan 27 (Print Publication: 2021).
DOI:	10.3389/fnmol.2021.804130
Abstrakt:	Glycogen synthase kinase 3 (GSK-3) is a Ser/Thr protein kinase that regulates many cellular processes, including synaptic plasticity. Previously, we reported that inhibition of GSK-3 prevents the induction of one of the major forms of synaptic plasticity, N-methyl-D-aspartate receptor (NMDAR)-dependent long-term depression (LTD), in hippocampal slices. In the present study, we have investigated the effects of inhibiting GSK-3 on learning and memory in healthy naïve animals. Systemic administration of a highly selective GSK-3 inhibitor, CT99021, reversibly blocked NMDAR-dependent LTD in the CA1 region of the hippocampus in anesthetized adult mice. In behavioral tasks, CT99021 had no effect on locomotor activity, anxiety, hippocampus-dependent contextual fear memory, and hippocampus-dependent reversal learning. However, CT99021 facilitated the rate of learning in the Morris water maze (MWM) and T-maze and enhanced the accuracy of long-term spatial memory in the MWM. These findings suggest that GSK-3 regulates the accuracy of spatial memory acquisition and recall. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Lee, Bortolotto, Bradley, Sanderson, Zhuo, Kaang and Collingridge.)
Databáze:	MEDLINE
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