Dynamic alterations in the central glutamatergic status following food and glucose intake: in vivo multimodal assessments in humans and animal models

Manabu Kubota, Yasuyuki Kimura, Masafumi Shimojo, Yuhei Takado, Joao M.N. Duarte, Hiroyuki Takuwa, Chie Seki, Hitoshi Shimada, Hitoshi Shinotoh, Keisuke Takahata, Soichiro Kitamura, Sho Moriguchi, Kenji Tagai, Takayuki Obata, Jin Nakahara, Yutaka Tomita, Masaki Tokunaga, Jun Maeda, Kazunori Kawamura, Ming Rong ZhangMasanori Ichise, Tetsuya Suhara, Makoto Higuchi

Research output: Contribution to journalArticlepeer-review

Abstract

Fluctuations of neuronal activities in the brain may underlie relatively slow components of neurofunctional alterations, which can be modulated by food intake and related systemic metabolic statuses. Glutamatergic neurotransmission plays a major role in the regulation of excitatory tones in the central nervous system, although just how dietary elements contribute to the tuning of this system remains elusive. Here, we provide the first demonstration by bimodal positron emission tomography (PET) and magnetic resonance spectroscopy (MRS) that metabotropic glutamate receptor subtype 5 (mGluR5) ligand binding and glutamate levels in human brains are dynamically altered in a manner dependent on food intake and consequent changes in plasma glucose levels. The brain-wide modulations of central mGluR5 ligand binding and glutamate levels and profound neuronal activations following systemic glucose administration were further proven by PET, MRS, and intravital two-photon microscopy, respectively, in living rodents. The present findings consistently support the notion that food-associated glucose intake is mechanistically linked to glutamatergic tones in the brain, which are translationally accessible in vivo by bimodal PET and MRS measurements in both clinical and non-clinical settings.

Original languageEnglish
JournalJournal of Cerebral Blood Flow and Metabolism
DOIs
Publication statusAccepted/In press - 2021

Keywords

  • glucose
  • glutamate
  • magnetic resonance spectroscopy
  • metabotropic glutamate receptor subtype 5
  • positron emission tomography

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

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