In vivo imaging of mGluR5 changes during epileptogenesis using [11C]ABP688 PET in pilocarpine-induced epilepsy rat model

PLoS One. 2014 Mar 24;9(3):e92765. doi: 10.1371/journal.pone.0092765. eCollection 2014.

Abstract

Introduction: Metabotropic glutamate receptor 5 (mGluR5) that regulates glutamatergic neurotransmission contributes to pathophysiology of epilepsy. In this study, we monitored the changes of mGluR5 in vivo using [11C]ABP688 PET during the epileptogenesis in a pilocarpine-induced epilepsy rat model.

Methods: In vivo mGluR5 images were acquired using [11C]ABP688 microPET/CT in pilocarpine-induced chronic epilepsy rat models and controls. We also acquired microPET/CT at acute, subacute as well as chronic periods after status epilepticus. Non-displaceable binding potential (BPND) of [11C]ABP688 was calculated using simplified reference tissue model in a voxel-based manner. mGluR5 BPND of the rat brains of epilepsy models and controls were compared.

Results: Status epilepticus developed after pilocarpine administration and was followed by recurrent spontaneous seizures for more than 3 weeks. In chronic epilepsy rat model, BPND in hippocampus and amygdala was reduced on a voxel-based analysis. Temporal changes of mGluR5 BPND was also found. In acute period after status epilepticus, mGluR5 BPND was reduced in the whole brain. BPND of caudate-putamen was restored in subacute period, while BPND of the rest of the brain was still lower. In chronic period, global BPND was normalized except in hippocampus and amygdala.

Conclusions: In vivo imaging of mGluR5 using [11C]ABP688 microPET/CT could successfully reveal the regional changes of mGluR5 binding potential of the rat brain in a pilocarpine-induced epilepsy model. The temporal and spatial changes in mGluR5 availability suggest [11C]ABP688 PET imaging in epilepsy provide abnormal glutamatergic network during epileptogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amygdala* / diagnostic imaging
  • Amygdala* / metabolism
  • Amygdala* / physiopathology
  • Animals
  • Epilepsy* / chemically induced
  • Epilepsy* / diagnostic imaging
  • Epilepsy* / metabolism
  • Epilepsy* / physiopathology
  • Hippocampus* / diagnostic imaging
  • Hippocampus* / metabolism
  • Hippocampus* / physiopathology
  • Male
  • Muscarinic Agonists / adverse effects*
  • Muscarinic Agonists / pharmacology
  • Oximes / pharmacology*
  • Pilocarpine / adverse effects*
  • Pilocarpine / pharmacology
  • Positron-Emission Tomography*
  • Pyridines / pharmacology*
  • Radiography
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Metabotropic Glutamate 5 / metabolism*
  • Synaptic Transmission / drug effects

Substances

  • 3-(6-methylpyridin-2-ylethynyl)cyclohex-2-enone-O-methyloxime
  • Grm5 protein, rat
  • Muscarinic Agonists
  • Oximes
  • Pyridines
  • Receptor, Metabotropic Glutamate 5
  • Pilocarpine

Grants and funding

This work was supported by the Nano-Biotechnology Project (Regenomics, 20100002086), WCU project (R31-2008-000-10103-0), the future-based technology development program (20100028755), Basic Science Research Program (2012R1A1A2008799, No. 2011-0030815, and No. 2008-0060169) through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (MEST) and a grant (kiom-2010-2) from the Inter-Institutional Collaboration Research Program provided by the Korea Research Council of Fundamental Science & Technology (KRCF), Korea. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.