Combined behavioral studies and in vivo imaging of inflammatory response and expression of mGlu5 receptors in schnurri-2 knockout mice.

Abstract

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.

• Authors: Ji-Kyung Choi, Aijun Zhu, Bruce G Jenkins, Satoko Hattori, Kun-Eek Kil, Tsuyoshi Takagi, Shunsuke Ishii, Tsuyoshi Miyakawa, Anna-Liisa Brownell
• Journal: Neuroscience letters (Neurosci Lett) Vol. 609 Pg. 159-64 (Nov 16 2015) ISSN: 1872-7972 [Electronic] Ireland
• PMID: 26483320 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• 3-fluoro-5-((pyridin-3-yl)ethynyl)benzonitrile
• Acetamides
• Carbon Radioisotopes
• Central Nervous System Stimulants
• DNA-Binding Proteins
• Fluorine Radioisotopes
• Grm5 protein, mouse
• Hivep2 protein, mouse
• N-(2-methoxybenzyl)-N-(4-phenoxypyridin-3-yl)acetamide
• Nitriles
• Pyridines
• Radiopharmaceuticals
• Receptor, Metabotropic Glutamate 5
• Methamphetamine
• Amphetamine

Topics

• Acetamides
• Amphetamine (pharmacology)
• Animals
• Brain (diagnostic imaging, metabolism)
• Carbon Radioisotopes
• Central Nervous System Stimulants (pharmacology)
• Cerebral Cortex (diagnostic imaging, metabolism)
• DNA-Binding Proteins (genetics)
• Disease Models, Animal
• Exploratory Behavior
• Fluorine Radioisotopes
• Hippocampus (diagnostic imaging, metabolism)
• Inflammation (diagnostic imaging, metabolism)
• Methamphetamine (pharmacology)
• Mice, Knockout
• Motor Activity
• Nitriles
• Positron-Emission Tomography
• Pyridines
• Radiopharmaceuticals
• Receptor, Metabotropic Glutamate 5 (metabolism)
• Schizophrenia (metabolism)