Altered Calcium Permeability of AMPA Receptor Drives NMDA Receptor Inhibition in the Hippocampus of Murine Obesity Models
Altered Calcium Permeability of AMPA Receptor Drives NMDA Receptor Inhibition in the Hippocampus of Murine Obesity Models
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DOI：
10.1007/s12035-022-02834-2
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发表时间：
2022-06-03
影响因子：
5.1
通讯作者：
Ishiuchi，Shogo
中科院分区：
文献类型：
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作者：
Miyagi，Yasuyo;Fujiwara，Kyoko;Ishiuchi，Shogo
越来越多的证据表明，青少年时期摄入更多的高脂肪饮食（HFD）会导致海马功能和形态发生改变；然而，这种现象背后的机制仍然难以捉摸。使用高分辨率结构成像结合分子和功能检测，小鼠断奶后用 HFD 治疗 12 周的肥胖小鼠模型显示谷氨酸介导的细胞内钙信号和活性发生变化，包括进一步选择性减少与记忆回忆障碍相关的海马灰质体积。非竞争性α-3-羟基-5-甲基-4-异恶唑丙酸受体（AMPAR）拮抗剂可恢复细胞内钙浓度失调，随后海马体积和记忆能力恢复正常，表明 AMPAR 可能作为肥胖相关认知衰退的一个有吸引力的治疗靶点。
Evidence has accumulated that higher consumption of high-fat diets (HFDs) during the juvenile/adolescent period induces altered hippocampal function and morphology; however, the mechanism behind this phenomenon remains elusive. Using high-resolution structural imaging combined with molecular and functional interrogation, a murine model of obesity treated with HFDs for 12 weeks after weaning mice was shown to change in the glutamate-mediated intracellular calcium signaling and activity, including further selective reduction of gray matter volume in the hippocampus associated with memory recall disturbance. Dysregulation of intracellular calcium concentrations was restored by a non-competitive α-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) antagonist, followed by normalization of hippocampal volume and memory recall ability, indicating that AMPARs may serve as an attractive therapeutic target for obesity-associated cognitive decline.