Combined behavioral studies and in vivo imaging of inflammatory response and expression of mGlu5 receptors in schnurri-2 knockout mice. (16th November 2015)

• Record Type: Journal Article
• Authors: Choi, Ji-Kyung; Zhu, Aijun; Jenkins, Bruce G.; Hattori, Satoko; Kil, Kun-Eek; Takagi, Tsuyoshi; Ishii, Shunsuke; Miyakawa, Tsuyoshi; Brownell, Anna-Liisa
• Is Part Of: Neuroscience letters. Volume 609(2015)
• Page Start: 159
• Page End: 164
• Publication Date: 2015-11-16
• Subjects: Schnurri-2 (Shn-2) knockout (KO) mice -- PET -- mGluR5 -- Inflammation -- Schizophrenia; Neurology -- Periodicals; Neurology -- Periodicals; Research -- Periodicals; Neurologie -- Périodiques; Neuroanatomie -- Périodiques; Neuropharmacologie -- Périodiques; Neurophysiologie -- Périodiques; Neurology; Periodicals; Electronic journals; 617.48
• DOI: 10.1016/j.neulet.2015.10.037
• Languages: English
• ISSNs: 0304-3940

Abstract

Highlights: In vivo PET imaging was used to investigate the schnurri-2 knockout mice. Increased inflammatory response was observed in several brain regions. Increased mGluR5 expression was observed in the cortex and hippocampus. Increased baseline activity was observed in open field locomotor test. Abnormal (decreased) activity was observed after psychostimulant challenge. 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.