Journal Article In Vivo Monitoring for Regional Changes of Metabotropic Glutamate Receptor Subtype 1 (mGluR1) in Pilocarpine-Induced Epileptic Rat Brain by Small-Animal PET

Yamasaki, Tomoteru  ,  Fujinaga, Masayuki  ,  Mori, Wakana  ,  Zhang, Yiding  ,  Wakizaka, Hidekatsu  ,  Nengaki, Nobuki  ,  Xie, Lin  ,  Hatori, Akiko  ,  Ming-Rong, Zhang

7 ( 1 )  , pp.14945-1 - 14945-9 , 2017-11 ,  Macmillan Publishers Limited, part of Springer Nature
Metabotropic glutamate receptor subtype 1 (mGluR1) is a crucial pharmacological target forseveral CNS disorders. In this study, we aimed to monitor in vivo regional changes ofmGluR1 related to neuroinflammation in the brains of rats after pilocarpine-induced statusepilepticus (PISE) using longitudinal positron emission tomography (PET). PISE was inducedin rats by administering lithium chloride, followed by repeated pilocarpine hydrochloridetreatments. PET assessments were conducted usingN-[4-[6-(isopropylamino)-pyrimidin-4-yl]-1,3-thiazol-2-yl]-N-methyl-4-[11C]methylbenzamide ([11C]ITDM), a selective radioligand for mGluR1, andN-benzyl-N-[11C]methyl-2-(7-methyl-8-oxo-2-phenyl-7,8-dihydro-9H-purin-9-yl)acetamide([11C]DAC), a selective translocator protein PET ligand for neuroinflammation monitoring.PET scans were conducted on PISE rats at 1 day (acute), 1 week (subacute) and 3 weeks(chronic) after repeated seizures. PET with [11C]ITDM showed significant decreases ofmGluR1 availability (BPND) in the thalamus and hippocampus after PISE over the chronicperiod. Conversely, PET with [11C]DAC exhibited a significant increase of radioactive uptakein the forebrain after the acute period, especially in the thalamus. These conflicting changes inthe thalamus indicated negative correlation. In conclusion, PET with [11C]ITDM couldsuccessfully visualize hippocampal and thalamic declines of mGluR1 related toneuroinflammation, which would help further understanding for mGluR1 functions inneuroexcitotoxicity.

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