title: Brain metabolite changes in subcortical regions after exposure to cuprizone for 6 weeks: potential implications for schizophrenia.
abstract: Cuprizone is a copper chelating agent able to selectively damage the white matter in the mouse brain. Recent studies have reported behavioral abnormalities relevant to some of schizophrenia symptoms. While associating white matter damage to the behavioral abnormalities, these previous studies did not rule out the possible impairment in neuronal functions in cuprizone-exposed mice. The aim of this study was to examine brain metabolites of the cuprizone-exposed mice by proton magnetic resonance spectroscopy ((1)H-MRS). The examined brain regions were the caudoputamen, midbrain, and thalamus; these subcortical regions showed different susceptibilities to cuprizone in terms of demyelination and oligodendrocyte loss in previous studies. Young C57BL/6 mice were fed a standard rodent chow without or with cuprizone (0.2 %) for 6 weeks. At the end, open-field and Y-maze tests were performed to measure the emotional and cognitive behaviors of the animals, followed by (1)H-MRS procedure to evaluate the brain metabolites. Cuprizone-exposure increased anxiety levels and impaired spatial working memory. The same treatment increased T2 signal intensity in the cerebral cortex, hippocampus, and caudoputamen, but not in the thalamus. Cuprizone-exposure decreased the concentrations of NAA and NAA+NAAG in caudoputamen, but not in thalamus and midbrain. It decreased levels of Cr+PCr, GPC+PCh and myo-inositol in all the three brain regions. These results provided neurochemical evidence for the impairment in neuronal functions by cuprizone treatment.
authors.affiliation: Department of Radiology, Second Affiliated Hospital, Shantou University Medical College, Shantou, 515041, Guangdong, China.
authors.forename: Gen
authors.initials: G
authors.lastname: Yan
authors.forename: Yinghua
authors.initials: Y
authors.lastname: Xuan
authors.forename: Zhuozhi
authors.initials: Z
authors.lastname: Dai
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Shen
authors.forename: Guishan
authors.initials: G
authors.lastname: Zhang
authors.forename: Haiyun
authors.initials: H
authors.lastname: Xu
authors.forename: Renhua
authors.initials: R
authors.lastname: Wu
mesh_terms: D000818:Animals; D001007:Anxiety / Q000139:chemically induced / Q000523:psychology; D001522:Behavior, Animal / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects*; D002614:Chelating Agents / Q000494:pharmacology*; D003071:Cognition / Q000187:drug effects; D003471:Cuprizone / Q000494:pharmacology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008570:Memory, Short-Term / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D012559:Schizophrenia / Q000378:metabolism*
chemical_list: D002614:Chelating Agents; D003471:Cuprizone