Sex-dependent changes in AMPAR expression and Na, K-ATPase activity in the cerebellum and hippocampus of α-Klotho-Hypomorphic mice

Aging is characterized by a functional decline in several physiological systems. α-Klotho-hypomorphic mice (Kl−/−) exhibit accelerated aging and cognitive decline. We evaluated whether male and female α-Klotho-hypomorphic mice show changes in the expression of synaptic proteins, N-methyl-d-aspartate...

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Published in:Neuropharmacology Vol. 258; p. 110097
Main Authors: dos Santos, Geovana Rosa Oliveira, Cararo-Lopes, Marina Minto, Possebom, Isabela Ribeiro, de Sá Lima, Larissa, Scavone, Cristoforo, Kawamoto, Elisa Mitiko
Format: Journal Article
Language:English
Published: England Elsevier Ltd 01-11-2024
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Summary:Aging is characterized by a functional decline in several physiological systems. α-Klotho-hypomorphic mice (Kl−/−) exhibit accelerated aging and cognitive decline. We evaluated whether male and female α-Klotho-hypomorphic mice show changes in the expression of synaptic proteins, N-methyl-d-aspartate receptor (NMDAR) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) subunits, postsynaptic density protein 95 (PSD-95), synaptophysin and synapsin, and the activity of Na+, K+-ATPase (NaK) isoforms in the cerebellum and hippocampus. In this study, we demonstrated that in the cerebellum, Kl−/− male mice have reduced expression of GluA1 (AMPA) compared to wild-type (Kl+/+) males and Kl−/− females. Also, Kl−/− male and female mice show reduced ɑ2/ɑ3-NaK and Mg2+-ATPase activities in the cerebellum, respectively, and sex-based differences in NaK and Mg2+-ATPase activities in both the regions. Our findings suggest that α-Klotho could influence the expression of AMPAR and the activity of NaK isoforms in the cerebellum in a sex-dependent manner, and these changes may contribute, in part, to cognitive decline. •Klotho-hypomorphic mice show sex-based reduced AMPAR expression in the cerebellum.•Male Klotho-hypomorphic mice show reduced α2/3-NaK activity in the cerebellum.•Female Klotho-hypomorphic mice show reduced Mg2+-ATPase activity in the cerebellum.•Klotho mice show sex-based distinct NaK activity in the cerebellum and hippocampus.
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ISSN:0028-3908
1873-7064
1873-7064
DOI:10.1016/j.neuropharm.2024.110097