RGS14414-Mediated Activation of the 14-3-3ζ in Rodent Perirhinal Cortex Induces Dendritic Arborization, an Increase in Spine Number, Long-Lasting Memory Enhancement, and the Prevention of Memory Deficits.

Autor:	Navarro-Lobato I; Laboratory of Neurobiology, CIMES, University of Malaga, Malaga 29010, Spain.; Department of Medicine, Faculty of Medicine, University of Malaga, Malaga 29010, Spain., Masmudi-Martín M; Laboratory of Neurobiology, CIMES, University of Malaga, Malaga 29010, Spain.; Department of Medicine, Faculty of Medicine, University of Malaga, Malaga 29010, Spain., López-Aranda MF; Laboratory of Neurobiology, CIMES, University of Malaga, Malaga 29010, Spain.; Department of Medicine, Faculty of Medicine, University of Malaga, Malaga 29010, Spain., Quiros-Ortega ME; Laboratory of Neurobiology, CIMES, University of Malaga, Malaga 29010, Spain.; Department of Medicine, Faculty of Medicine, University of Malaga, Malaga 29010, Spain., Carretero-Rey M; Laboratory of Neurobiology, CIMES, University of Malaga, Malaga 29010, Spain.; Department of Medicine, Faculty of Medicine, University of Malaga, Malaga 29010, Spain., Garcia-Garrido MF; Laboratory of Neurobiology, CIMES, University of Malaga, Malaga 29010, Spain.; Department of Medicine, Faculty of Medicine, University of Malaga, Malaga 29010, Spain., Gallardo-Martínez C; Laboratory of Neurobiology, CIMES, University of Malaga, Malaga 29010, Spain.; Department of Medicine, Faculty of Medicine, University of Malaga, Malaga 29010, Spain., Martín-Montañez E; Department of Pharmacology, Faculty of Medicine, University of Malaga, Malaga 29010, Spain., Gaona-Romero C; Laboratory of Neurobiology, CIMES, University of Malaga, Malaga 29010, Spain.; Department of Medicine, Faculty of Medicine, University of Malaga, Malaga 29010, Spain., Delgado G; Laboratory of Neurobiology, CIMES, University of Malaga, Malaga 29010, Spain.; Department of Medicine, Faculty of Medicine, University of Malaga, Malaga 29010, Spain., Torres-Garcia L; Laboratory of Neurobiology, CIMES, University of Malaga, Malaga 29010, Spain.; Department of Medicine, Faculty of Medicine, University of Malaga, Malaga 29010, Spain., Terrón-Melguizo J; Laboratory of Neurobiology, CIMES, University of Malaga, Malaga 29010, Spain.; Department of Medicine, Faculty of Medicine, University of Malaga, Malaga 29010, Spain., Posadas S; Laboratory of Neurobiology, CIMES, University of Malaga, Malaga 29010, Spain.; Department of Medicine, Faculty of Medicine, University of Malaga, Malaga 29010, Spain., Muñoz LR; Laboratory of Neurobiology, CIMES, University of Malaga, Malaga 29010, Spain.; Department of Medicine, Faculty of Medicine, University of Malaga, Malaga 29010, Spain., Rios CV; Laboratory of Neurobiology, CIMES, University of Malaga, Malaga 29010, Spain.; Department of Medicine, Faculty of Medicine, University of Malaga, Malaga 29010, Spain., Zoidakis J; Biotechnology Division, Biomedical Research Foundation of the Academy of Athens, Athens 11527, Greece., Vlahou A; Biotechnology Division, Biomedical Research Foundation of the Academy of Athens, Athens 11527, Greece., López JC; Animal Behavior and Neuroscience Lab., Department of Experimental Psychology, Faculty of Psychology, University of Seville, Seville 41018, Spain., Khan ZU; Laboratory of Neurobiology, CIMES, University of Malaga, Malaga 29010, Spain.; Department of Medicine, Faculty of Medicine, University of Malaga, Malaga 29010, Spain.; CIBERNED, Institute of Health Carlos III, Madrid 28031, Spain.
Jazyk:	angličtina
Zdroj:	Cerebral cortex (New York, N.Y. : 1991) [Cereb Cortex] 2022 Apr 20; Vol. 32 (9), pp. 1894-1910.
DOI:	10.1093/cercor/bhab322
Abstrakt:	The remedy of memory deficits has been inadequate, as all potential candidates studied thus far have shown limited to no effects and a search for an effective strategy is ongoing. Here, we show that an expression of RGS14414 in rat perirhinal cortex (PRh) produced long-lasting object recognition memory (ORM) enhancement and that this effect was mediated through the upregulation of 14-3-3ζ, which caused a boost in BDNF protein levels and increase in pyramidal neuron dendritic arborization and dendritic spine number. A knockdown of the 14-3-3ζ gene in rat or the deletion of the BDNF gene in mice caused complete loss in ORM enhancement and increase in BDNF protein levels and neuronal plasticity, indicating that 14-3-3ζ-BDNF pathway-mediated structural plasticity is an essential step in RGS14414-induced memory enhancement. We further observed that RGS14414 treatment was able to prevent deficits in recognition, spatial, and temporal memory, which are types of memory that are particularly affected in patients with memory dysfunctions, in rodent models of aging and Alzheimer's disease. These results suggest that 14-3-3ζ-BDNF pathway might play an important role in the maintenance of the synaptic structures in PRh that support memory functions and that RGS14414-mediated activation of this pathway could serve as a remedy to treat memory deficits. (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
Databáze:	MEDLINE
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