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

IF 4.6 2区医学 Q1 NEUROSCIENCES Neuropharmacology Pub Date : 2024-07-31 DOI:10.1016/j.neuropharm.2024.110097

Geovana Rosa Oliveira dos Santos , Marina Minto Cararo-Lopes , Isabela Ribeiro Possebom , Larissa de Sá Lima , Cristoforo Scavone , Elisa Mitiko Kawamoto

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Abstract

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.

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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

衰老的特征是多个生理系统的功能衰退。α-Klotho-hypomorphic小鼠（Kl-/-）表现出加速衰老和认知能力下降。我们评估了雌雄α-Klotho-hypomorphic小鼠的突触蛋白、N-甲基-D-天冬氨酸受体（NMDAR）和α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体（AMPAR）亚基的表达是否发生了变化、突触后密度蛋白 95（PSD-95）、突触蛋白和突触素，以及小脑和海马中 Na+、K+-ATPase（NaK）同工酶的活性。本研究表明，在小脑中，与野生型（Kl+/+）雄性小鼠和Kl-/-雌性小鼠相比，Kl-/-雄性小鼠的GluA1（AMPA）表达量减少。此外，Kl-/-雄性和雌性小鼠小脑中的ɑ2/ɑ3-NaK和Mg2+-ATPase活性也分别降低，而且这两个区域的NaK和Mg2+-ATPase活性也存在性别差异。我们的研究结果表明，α-Klotho可能以性别依赖的方式影响小脑中AMPAR的表达和NaK同工酶的活性，而这些变化可能是认知能力下降的部分原因。

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来源期刊

Neuropharmacology 医学-神经科学

CiteScore

10.00

自引率

4.30%

发文量

288

审稿时长

45 days

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).