Miyagi Yasuyo, Fujiwara Kyoko, Hikishima Keigo, Utsumi Daisuke, Katagiri Chiaki, Nishimura Masahiko, Takagi Hiroshi, Ishiuchi Shogo
Department of Neurosurgery, Graduate School of Medicine, University of the Ryukyus, 207 Uehara, Nishihara-machi, Okinawa, 903-0215, Japan.
Animal Resources Section, Okinawa Institute of Science and Technology Graduate University, 1919-1 Tancha, Onna-son, Kunigami, Okinawa, 904-0495, Japan.
Mol Neurobiol. 2022 Aug;59(8):4902-4925. doi: 10.1007/s12035-022-02834-2. Epub 2022 Jun 3.
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.
越来越多的证据表明，在幼年/青少年时期大量摄入高脂肪饮食（HFDs）会导致海马体功能和形态发生改变；然而，这一现象背后的机制仍不清楚。通过高分辨率结构成像结合分子和功能研究，断奶小鼠用HFDs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，包括与记忆回忆障碍相关的海马体灰质体积进一步选择性减少。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的失调，随后海马体体积和记忆回忆能力恢复正常，这表明AMPARs可能是肥胖相关认知衰退的一个有吸引力的治疗靶点。
