Publication
Title
Multiprobe molecular imaging of an NMDA receptor hypofunction rat model for glutamatergic dysfunction
Author
Abstract
There are many indications of a connection between abnormal glutamate transmission through N-methyl-d-aspartate (NMDA) receptor hypofunction and the occurrence of schizophrenia. The importance of metabotropic glutamate receptor subtype 5 (mGluR5) became generally recognized due to its physical link through anchor proteins with NMDAR. Neuroinflammation as well as the kynurenine (tryptophan catabolite; TRYCAT) pathway are equally considered as major contributors to the pathology. We aimed to investigate this interplay between glutamate release, neuronal activation and inflammatory markers, by using small-animal positron emission tomography (PET) in a rat model known to induce schizophrenia-like symptoms. Daily intraperitoneal injection of MK801 or saline were administered to induce the model together with N-Acetyl-cysteine (NAc) or saline as the treatment in 24 male Sprague Dawley rats for one month. Biweekly in vivo [11C]-ABP688 microPET was performed together with mGluR5 immunohistochemistry. Simultaneously, weekly in vivo [18F]-FDG microPET imaging data for glucose metabolism was acquired and microglial activation was investigated with biweekly in vivo [18F]-PBR111 scans versus OX42 immunohistochemistry. Finally, plasma samples were analyzed for TRYCAT metabolites. We show that chronic MK801 administration (and thus elevated endogenous glutamate) causes significant tissue loss in rat brain, enhances neuroinflammatory pathways and may upregulate mGluR5 expression.
Language
English
Source (journal)
Psychiatry research: neuroimaging / International Society for Neuroimaging in Psychiatry. - Limerick
Publication
Limerick : 2016
ISSN
0925-4927
Volume/pages
248(2016), p. 1-11
ISI
000369712800001
Full text (Publisher's DOI)
Full text (open access)
Full text (publisher's version - intranet only)
UAntwerpen
Faculty/Department
Research group
[E?say:metaLocaldata.cgzprojectinf]
Multimodal investigation of a neuroinflammatory model in schizophrenia.
Design, synthesis and evaluation of new potent radioligands for PDE7 imaging and implication of PDE7 in neurological disorders.
Investigation of functional and structural brain abnormalities utilizing multimodal brain imaging in a neurodevelopmental animal model with relevance to schizophrenia.
Publication type
Subject
Affiliation
Publications with a UAntwerp address
External links
Web of Science
Record
Identification
Creation 31.03.2016
Last edited 13.08.2017
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