会議発表用資料 Alterations of central metabotropic glutamate receptor 5 binding and glutamate concentrations by food intake

久保田, 学  ,  木村, 泰之  ,  市瀬, 正則  ,  関, 千江  ,  島田, 斉  ,  篠遠, 仁  ,  高畑, 圭輔  ,  北村, 聡一郎  ,  森口, 翔  ,  石井, 辰弥  ,  互, 健二  ,  高堂, 裕平  ,  佐野, ひろみ  ,  小畠, 隆行  ,  徳永, 正希  ,  前田, 純  ,  張, 明栄  ,  須原, 哲也  ,  樋口, 真人

2018-06-19
内容記述
Glutamatergic neurotransmission in the brain is coupled with cerebral and possibly with systemic glucose metabolism, which could be affected by food intake. The current study aimed to investigate effects of food intake on metabotropic glutamate receptor 5 (mGluR5) binding and glutamate levels in the brains of living subjects. Eleven healthy males underwent two clinical PET scans 3 hours apart using (E)-[11C]ABP688, a radioligand for mGluR5. Imaging sessions were performed with (n=5) or without (n=6) food intake between the two scans. Two MRS scans were also conducted, one before the first and the other after the second PET scan. Arterial blood was sampled during the PET scans to estimate mGluR5 binding as total distribution volume (VT). Glutamate concentrations in the right anterior and posterior insulae were measured using MRS data. To support the clinical PET findings, four awake rats underwent two PET scans on different days, one under control condition and the other under glucose-load (2g/kg p.o.) condition. In assays of human subjects with food intake, VT increased in the whole brain by 29% on average (p = 0.01) and glutamate concentrations in the right posterior insula increased by 10% (p = 0.02) between the first and second scans. By contrast, VT decreased by 20% on average (p = 0.02) and glutamate concentrations decreased by 8% (p = 0.01) in the corresponding areas of subjects without food intake. Cerebral VT was significantly and positively correlated with the blood glucose level (Pearson’s r = 0.87, p = 0.001). In the rat experiment, intake of glucose alone was sufficient to increase mGluR5 binding by 18%. These results indicate that plasma glucose levels are intimately involved in the dynamic activities of glutamate neurons represented by the mGluR5 status and glutamate metabolism in the brain, as cerebral glutamate neurotransmitter cycling is concurrent with aerobic glycolysis.
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