| Schizophrenia is a severe mental illness, which is suspective in youngadults. Schizophrenia affects the healthy and future life of patients, whichbrings heavy burden on the patients and their families, as well as the society.However the cause of schizophrenia have not been elucidated completely.Post-mortem studies and image technology studies found thatschizophrenia patients had abnormalities in corpus callosum volme andintegrity of the nerve fibers in corpus callosum. Cuprizon [CPZ,Bis(Cyclohexylidenehydrazide)] is a copper chelating agent, which caninduce mice schizophrenia-like behaviors in mice and the demyelination ofmouse brain. We used behavioral tests to investigate the behavioraldifferencese between CPZ-treated mice and Control mice. Then, we uesdthe new stereological methods and transmission electron microscopetechnique to investigate the corpus callosum and the myelinated nervefibers in corpus callosum. We analysed the relationship between thedemyelination of the myelinated nerve fibers and abnormal behaviors inorder to provide further theoretical bases for the oligodenrocyte damge hypothesis of schizophrenia and scientific evidences for effective therapyof schizophrenia.Part One1.Materials and methods1.119male6-week-old C57BL/6mice were diveded into CPZ-treatedgroup (n=9) and Control group (n=10). CPZ-treated group were fed withrodent chow mixed with0.2%CPZ (w/w) and distilled water for6weeksand Control group were fed with standard rodent chow and distilled waterfor6weeks too. Mice were weighted each2-3days.1.2After6weeks, behavioral tests, including Open field test, Evelatedplus maze test, Morris water maze test, Rota-rod test and Hole-board test,were held to detect the behaviour changes of two groups.2.Results2.1The body weight was increased in Control group, but the bodyweight was decreased in CPZ-treated group in the first week fed with CPZ.Although the weight of CPZ-treated group was raised again and kept instabilized state, but the body weight of CPZ-treated group was stillsignificantly lower than the Control group (P＜0.05).2.2CPZ-treated group spent more time in the centre area in Open fieldtest and more time in the open arms in Elevated plus maze than Controlgroup (P＜0.05). There were no significant differences between two groups in the results of Morris water maze, Rota-rod test and Hole-board test.Part Two1.Materials and methods1.15mice were randomly chosen from each group when they finishedthe behavioral tests. One hemisphere was sampled from each mouse brain.Then the hemispheres were cut into4μ m paraffin sections andimmumohistochenmical stainning was made with anti-MBP.1.2The other hemispheres were coronally cut into sequential1mmslabs, and the cut slabs were photographed under anatomic microscope witha magnification of10.1.33-5tissue blocks were randomly sampled from corpus callosum ina systematic random fashion. One ultra-thin section was cut from eachsampled block. From each cut section,5-10fields of view were randomlyphotographed under transmission electron microscope with a magnificationof6000or20000.1.4In the CPZ-treated group and Control group, the corpus callosumvolume, the length density and total length, the volume density and totalvolum, the inner circumference and outer circumference and the meandiameter of the myelinated nerve fibers in corpus callosum wereinvestigated with the new stereological methods. 2.Results2.1The results of immumohistochemical staining showed lighterstaining and less fibers from corpus callosum to cortex in CPZ-treatedgroup than Control group.2.2The results of transmission electron microscope indicated damageof myelin sheath ultrastructure in CPZ-treated group: lytic and destroyedsheaths, separtion of sheath and axon, vacuolization in sheaths and damagein axons.2.3There was no significant difference in the corpus callosum volumebetween CPZ-treated group and Control group. The length density and totallength of the myelinated nerve fibers in the corpus callosum of CPZ-treatedgroup were significantly decreased than those of Control group (P＜0.05).2.4The volume of axons in the myelinated nerve fibers in corpuscallosum was significantly decreased in CPZ-treated group when comparedto Control group (P＜0.05), but there were no significant differencesbetween two groups in total volume of myelinated nerve fibers and the totalvolume of the myelinated sheath in the corpus callosum (P＞0.05).2.5There were no significant differences in inner circumference andouter circumferences of the myelinated nerve fibers in the corpus callosumbetween CPZ-treated group and Control group (P＞0.05).2.6There were no significant differences in diameter of themyelinated nerve fibers and the diameter of axons in the myelinated nervefibers in the corpus callosum between CPZ-treated group and Contol group (P＞0.05).2.7When compared to the control group, the total length of themyelinated nerve fibers with the diameter of0.4-0.8in CPZ-treated groupwas significant decreased (P＜0.05), while the total length of themyelinated fibers with the diameter of1.4-1.8μm in CPZ-treated groupwas significantly increased. When compared to the Control group, the totallength of the myelinated nerve fibers with the axon diameter of0.4-1.0μmin CPZ-treated group were significantly decreased (P＜0.05).General conclusions1. The present study demonstrated that CPZ model mice could displaya series of schizophrenia-like symptoms, which could be a efficient animalmodel to study schizophrenia.2. Combining transmission electron microscope technique withstereological methods, we quantitatively investigated the corpus callosumand the myelinated nerve fibers in the corpus callosum of CPZ-treatedgroup and Control group. Our results would privide important referencevalues for the future studies on the changes of the corpus callosum inschizophrenia.3. When compared to the Control group, the total length of themyelinated nerve fibers in corpus callosum was significantly decreased inCPZ-treated group. The loss of the total length of the myelinated nervefibers in CPZ-treated group was mainly due to the loss of myelinated nerve fibers with the diameter of0.4-0.8μm.4. There were no significant differences in the corpus callosumvolume, the volume of the myelinted nerve fibers and the myelin sheaths inthe corpus callosum between CPZ-treated group and Control group. Thevolume of the axons in the myelinated nerve fibers in the corpus callosumof CPZ-treated group was significantly decreased when compared to theControl group. |
PDF Full Text Request