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. 2022 Aug;59(8):4902-4925.
doi: 10.1007/s12035-022-02834-2. Epub 2022 Jun 3.

Altered Calcium Permeability of AMPA Receptor Drives NMDA Receptor Inhibition in the Hippocampus of Murine Obesity Models

Yasuyo Miyagi  1 , Kyoko Fujiwara  1 , Keigo Hikishima  2 , Daisuke Utsumi  3 , Chiaki Katagiri  1 , Masahiko Nishimura  1 , Hiroshi Takagi  1 , Shogo Ishiuchi  4
Affiliations

Altered Calcium Permeability of AMPA Receptor Drives NMDA Receptor Inhibition in the Hippocampus of Murine Obesity Models

Yasuyo Miyagi et al. Mol Neurobiol. 2022 Aug.

Abstract

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.

Keywords: CP-AMPAR; Cognitive function; NMDAR; Obesity.

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