Abstract：Objective To investigate the behavioral and neurochemical alterations in mice exposed to cuprizone.MethodsC57BL/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=5000/10/2.2ms) was used to measure in vivo proton spectra from the left striatum (voxel volume:8μL) and thalamus (27μL) 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.ResultsCPZ-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.ConclusionsCPZ-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.
