To investigate the behavioral and neurochemical alterations in mice exposed to cuprizone.

C57BL/6 mice were given 0.2% CPZ-containing diet for 4 weeks while controls ate the same diet without CPZ.The animals were subjected to behavioral tests, T2WI and ¹HMRS scan.An ultra short echo stimulated echo acquisition (STEAM) localization sequence (TR/TM/TE=5 000/10/2.2 ms) was used to measure in vivo proton spectra from the left striatum (voxel volume: 8 μL) and thalamus (27 μL) of C57BL/6 mice at 7.0T and acquired proton spectra post-processed offline with LCModel.The difference of the T2WI signal intensity was compared with independent sample t-test, and the difference of neurochemical alterations was compared with one-way analysis of variance.

CPZ-fed mice showed significant decrease of spontaneous alternation in the Y-maze test[295.430±83.250)cm, (257.440±75.430)cm, t=0.031, P<0.05]. In quantitative analysis of visual, lateral ventricle volume in CPZ-fed mice was larger than that in control mice, and the difference was statistically significant[(0.980±0.050)mm², (0.890±0.470)mm², t=5.670, P<0.05]. The signal of intensity in the CTX(0.787±0.015, 0.628±0.027), CPU (0.732±0.012, 0.628±0.021) and Hip (0.745±0.021, 0.620±0.022) were significantly high in CPZ-fed mice(t=0.880, 0.003, 0.027; P<0.05). The concentrations of N-acetyl aspartate (NAA, 4.217±0.488), N-acetyl aspartate + N-acety laspartyl glutamate (NAA+ NAAG, 4.236±0.389) in the left striatum and thalamus were significantly reduced in CPZ-fed mice(t=9.014, 10.990; P<0.05). In addition, the concentration of Glu+ Gln (5.147±0.477, t=7.307, P<0.05) in the left thalamus of CPZ-fed mice was significantly lower than that in control mice.The concentrations of Cr+ PCr (4.415±0.527) and MI (3.737±0.428) in thalamus were significantly reduced in CPZ-fed mice(t=9.120, 5.911; P<0.05). There were no satitistically significant difference in levels of rest metabolites.

CPZ-fed mice show deficit in working memory as indicated by Y-maze test and have a higher Glx level in their thalamus.Higher signal intensity of T2WI and lower NAA and NAA+ NAAG levels may reflect an overall reduction of cellular processes in the brain of CPZ-fed mice, which may be related to demyelination and oligodendrocyte loss.The results prompt that the CPZ processing model can be served as potential animal model of schizophrenia in mice.