Concurrent changes in 1H MRS metabolites and antioxidant enzymes in the brain of C57BL/6 mouse short-termly exposed to cuprizone: Possible implications for schizophrenia

• CPZ-exposure for 7 days caused an anxiety-like behavior in C57BL/6 mice.
• It decreased GPC + PCh, ml, NAA, NAA + NAAG, and PCr in the thalamus and hippocampus.
• The treatment increased levels of GABA in the two brain regions.
• It reduced the activities of total SOD in CTX and of Mn-SOD in CP.
• It reduced the activities of catalase and GSH-Px in the hippocampus.

Cuprizone (CPZ) is a copper chelating agent able to selectively insult mature oligodendrocytes (OLs) in brains of rodents. The CPZ-exposed mice show behavioral changes and have been employed to examine a putative role of altered OLs in the pathophysiology of schizophrenia. The aims of this study were to examine the brain metabolites in the CPZ-exposed mice during the early stage and to measure some antioxidant enzymes, lipid peroxidation and hydrogen peroxide (H2O2) in brain tissue.C57BL/6 mice were fed normal or CPZ-containing diet for 7 days. On days 7 and 8, mice were subjected to behavioral tests. On days 9 and 10, mice were subjected to 1H MRS procedure. On day 10 mice were sacrificed and their brain tissue was processed for biochemical analyses. CPZ-exposure for 7 days caused an anxiety-like behavior, but had no effect on the social interaction and spatial working memory in C57BL/6 mice. The treatment significantly decreased levels of GPC + PCh, ml, NAA, NAA + NAAG, and PCr in the thalamus and hippocampus. It impaired the activities of some antioxidant enzymes, but did not increase levels of MDA and H2O2.This first 1H MRS study with CPZ-exposed mice provided neurochemical evidence for mitochondrial dysfunction in brain cells of living mice during the early stage of CPZ-exposure. The results are of relevance to the pathophysiology of schizophrenia in which mitochondrial dysfunction of neural cells and altered OLs are two important players.