{"title":"α-Klotho-Hypomorphic小鼠小脑和海马中AMPAR表达和Na、K-ATP酶活性的性别依赖性变化","authors":"","doi":"10.1016/j.neuropharm.2024.110097","DOIUrl":null,"url":null,"abstract":"<div><p>Aging is characterized by a functional decline in several physiological systems. α-Klotho-hypomorphic mice (Kl<sup>−/−</sup>) 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-<span>d</span>-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<sup>+</sup>, K<sup>+</sup>-ATPase (NaK) isoforms in the cerebellum and hippocampus. In this study, we demonstrated that in the cerebellum, Kl<sup>−/−</sup> male mice have reduced expression of GluA1 (AMPA) compared to wild-type (Kl<sup>+/+</sup>) males and Kl<sup>−/−</sup> females. Also, Kl−/− male and female mice show reduced ɑ2/ɑ3-NaK and Mg<sup>2+</sup>-ATPase activities in the cerebellum, respectively, and sex-based differences in NaK and Mg<sup>2+</sup>-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.</p></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":null,"pages":null},"PeriodicalIF":4.6000,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Sex-dependent changes in AMPAR expression and Na, K-ATPase activity in the cerebellum and hippocampus of α-Klotho-Hypomorphic mice\",\"authors\":\"\",\"doi\":\"10.1016/j.neuropharm.2024.110097\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Aging is characterized by a functional decline in several physiological systems. α-Klotho-hypomorphic mice (Kl<sup>−/−</sup>) 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-<span>d</span>-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<sup>+</sup>, K<sup>+</sup>-ATPase (NaK) isoforms in the cerebellum and hippocampus. In this study, we demonstrated that in the cerebellum, Kl<sup>−/−</sup> male mice have reduced expression of GluA1 (AMPA) compared to wild-type (Kl<sup>+/+</sup>) males and Kl<sup>−/−</sup> females. Also, Kl−/− male and female mice show reduced ɑ2/ɑ3-NaK and Mg<sup>2+</sup>-ATPase activities in the cerebellum, respectively, and sex-based differences in NaK and Mg<sup>2+</sup>-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.</p></div>\",\"PeriodicalId\":19139,\"journal\":{\"name\":\"Neuropharmacology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.6000,\"publicationDate\":\"2024-07-31\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Neuropharmacology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0028390824002661\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"NEUROSCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Neuropharmacology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0028390824002661","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
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 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.
期刊介绍：
Neuropharmacology publishes high quality, original research and review articles within the discipline of neuroscience, especially articles with a neuropharmacological component. However, papers within any area of neuroscience will be considered. The journal does not usually accept clinical research, although preclinical neuropharmacological studies in humans may be considered. The journal only considers submissions in which the chemical structures and compositions of experimental agents are readily available in the literature or disclosed by the authors in the submitted manuscript. Only in exceptional circumstances will natural products be considered, and then only if the preparation is well defined by scientific means. Neuropharmacology publishes articles of any length (original research and reviews).
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