Abstract
This study quantitatively measured the changes in metabolites in the hippocampal lesions of a rat model of cuprizone-induced demyelination as detected using in vivo 7 T proton magnetic resonance spectroscopy. Nineteen Sprague Dawley rats were randomly divided into two groups and fed a normal chow diet or cuprizone (0.2%, w/w) for 7 weeks. Demyelinated hippocampal lesions were quantitatively measured using a 7 T magnetic resonance imaging scanner. All proton spectra were quantified for metabolite concentrations and relative ratios. Compared to those in the controls, the cuprizone-induced rats had significantly higher concentrations of glutamate (p = 0.001), gamma-aminobutyric acid (p = 0.019), and glutamate + glutamine (p = 0.001); however, creatine + phosphocreatine (p = 0.006) and myo-inositol (p = 0.001) concentrations were lower. In addition, we found that the glutamine and glutamate complex/total creatine (p < 0.001), glutamate/total creatine (p < 0.001), and GABA/total creatine (p = 0.002) ratios were significantly higher in cuprizone-treated rats than in control rats. Our results showed that cuprizone-induced neuronal demyelination may influence the severe abnormal metabolism in hippocampal lesions, and these responses could be caused by microglial activation, mitochondrial dysfunction, and astrocytic necrosis.
Highlights
Multiple sclerosis (MS) is a chronic and progressive inflammatory disease of the central nervous system (CNS) [1,2]
To induce demyelination in the hippocampus, eight CPR rats were fed a milled diet with 0.2% cuprizone for 7 weeks, while CTRL rats were maintained on a regular chow diet
Representative high-resolution 7 T spectra with narrow linewidths from a single voxel of the hippocampal region were obtained throughout the study
Summary
Multiple sclerosis (MS) is a chronic and progressive inflammatory disease of the central nervous system (CNS) [1,2]. Studies have shown that demyelination affects the white matter (WM) in the corpus callosum and the gray matter (GM), such as that in the cortex, hippocampus, and cerebellum [5,6]. Among these brain regions, the hippocampus plays a pivotal role in learning processes, spatial memory, and the consolidation of long-term memory from short-term memory [7,8]. Cuprizone is a selective and sensitive copper chelating agent that is commonly used to create a toxicity-induced non-autoimmune animal model of MS to assess the pathophysiological processes of cerebral demyelination and remyelination [3]. We used a well-characterized cuprizoneinduced MS model to investigate the neurochemical changes in the hippocampal region
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
