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

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 (1)H 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 (1)H 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.