Combined behavioral studies and in vivo imaging of inflammatory response and expression of mGlu5 receptors in schnurri-2 knockout mice.
Schnurri-2 (Shn-2) knockout (KO) mice have been proposed as a preclinical neuroinflammatory schizophrenia model. We used behavioral studies and imaging markers that can be readily translated to human populations to explore brain effects of inflammation. Shn-2 KO mice and their littermate control mice were imaged with two novel PET ligands; an inflammation marker [(11)C]PBR28 and the mGluR5 ligand [(18)F]FPEB. Locomotor activity was measured using open field exploration with saline, methamphetamine or amphetamine challenge. A significantly increased accumulation of [(11)C]PBR28 was found in the cortex, striatum, hippocampus and olfactory bulb of Shn-2 KO mice. Increased mGluR5 binding was also observed in the cortex and hippocampus of the Shn-2 KO mice. Open field locomotor testing revealed a large increase in novelty-induced hyperlocomotion in Shn-2 KO mice with abnormal (decreased) responses to either methamphetamine or amphetamine. These data provide additional support to demonstrate that the Shn-2 KO mouse model exhibits several behavioral and pathological markers resembling human schizophrenia making it an attractive translational model for the disease.
Martinos Center for Biomedical Imaging, Department of Radiology, MGH and Harvard Medical School, Charlestown, MA 02129, USA.
Ji-Kyung
JK
Choi
Martinos Center for Biomedical Imaging, Department of Radiology, MGH and Harvard Medical School, Charlestown, MA 02129, USA.
Aijun
A
Zhu
Martinos Center for Biomedical Imaging, Department of Radiology, MGH and Harvard Medical School, Charlestown, MA 02129, USA.
Bruce G
BG
Jenkins
Division of Systems Medical Science, Institute for Comprehensive Medical Science, Fujita Health University, Toyoake, Japan; Japan Science and Technology Agency, CREST, Kawaguchi, Japan.
Satoko
S
Hattori
Martinos Center for Biomedical Imaging, Department of Radiology, MGH and Harvard Medical School, Charlestown, MA 02129, USA.
Kun-Eek
KE
Kil
RIKEN Tsukuba Institute, Tsukuba, Japan; Institute for Developmental Research, Aichi Human Service Center, Kasugai, Japan.
Tsuyoshi
T
Takagi
Japan Science and Technology Agency, PRESTO, Kawaguchi, Japan.
Shunsuke
S
Ishii
Division of Systems Medical Science, Institute for Comprehensive Medical Science, Fujita Health University, Toyoake, Japan; Section of Behavior Patterns, Center for Genetic Analysis of Behavior, National Institute for Physiological Sciences, Okazaki, Japan; Japan Science and Technology Agency, CREST, Kawaguchi, Japan.
Tsuyoshi
T
Miyakawa
Martinos Center for Biomedical Imaging, Department of Radiology, MGH and Harvard Medical School, Charlestown, MA 02129, USA. Electronic address: abrownell@mgh.harvard.edu.
Anna-Liisa
AL
Brownell
D000081:Acetamides; D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism; D002250:Carbon Radioisotopes; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics*; D004195:Disease Models, Animal; D005106:Exploratory Behavior; D005462:Fluorine Radioisotopes; D006624:Hippocampus / Q000000981:diagnostic imaging / Q000378:metabolism; D007249:Inflammation / Q000000981:diagnostic imaging / Q000378:metabolism; D008694:Methamphetamine / Q000494:pharmacology; D018345:Mice, Knockout; D009043:Motor Activity; D009570:Nitriles; D049268:Positron-Emission Tomography; D011725:Pyridines; D019275:Radiopharmaceuticals; D064529:Receptor, Metabotropic Glutamate 5 / Q000378:metabolism*; D012559:Schizophrenia / Q000378:metabolism
C527000:3-fluoro-5-((pyridin-3-yl)ethynyl)benzonitrile; D000081:Acetamides; D002250:Carbon Radioisotopes; D000697:Central Nervous System Stimulants; D004268:DNA-Binding Proteins; D005462:Fluorine Radioisotopes; C578936:Grm5 protein, mouse; C490430:Hivep2 protein, mouse; C526798:N-(2-methoxybenzyl)-N-(4-phenoxypyridin-3-yl)acetamide; D009570:Nitriles; D011725:Pyridines; D019275:Radiopharmaceuticals; D064529:Receptor, Metabotropic Glutamate 5; D008694:Methamphetamine; D000661:Amphetamine
Inflammation; PET; Schizophrenia; Schnurri-2 (Shn-2) knockout (KO) mice; mGluR5