精神分裂症模型大鼠青春期脑内胶质细胞及白质的变化

Changes of glial cells and white matter in pubescent stage of schizophrenia rats

目的探讨青春期免疫反应在孕期感染聚肌胞苷酸（Polyfiboinosinic—polyribocytidilicacid，PolyI：C）所致子代精神分裂症动物模型中的变化和对脑白质的影响。方法育种获得孕鼠随机分为模型组（n=6）和对照组（n=5），分别于孕9d给予尾静脉注射10mr,／kgpoly（I：C）和等体积的0．9％生理盐水。模型组（n=9）和对照组（n=7）仔鼠于6周龄时采用免疫组化技术检测小胶质细胞和星形胶质细胞在额叶和海马的变化，劳克坚牢蓝（LuxolFastBlue，LFB）染色法观察脑白质变化；另选取模型组（n=10）和对照组（n=10）仔鼠于8周龄时进行行为学评估。结果模型组仔鼠成年早期前脉冲抑制实验中模型组的PP2、PP4和PP8均分别小于对照组（P〈0．01）；被动规避实验中模型组的Tl大于对照组，T小于对照组（P〈0．01）；青春期时模型组仔鼠额叶和海马的小胶质细胞数量[（264±33）个/mm2，（271±38）个／mm2]较对照组[（140±29）个／mm2，（169±37）个／mm2]明显升高，伴有显著形态学变化（P〈0．01），额叶和海马的星形胶质细胞蛋白表达的光密度值与对照组相比无明显变化（P〉0．05）；青春期模型组仔鼠胼胝体部位光密度值（0．29±0．02）较对照组（0．33±0．03）低（P〈0．01）。结论孕期感染poly（I：C）致子代大鼠模型成年期有明显的类精神分裂症样行为，子代青春期大鼠脑内存在小胶质细胞活化以及脑白质脱髓鞘的变化，进一步为精神分裂症病理机制中神经炎性反应和脑白质之间的关系提供了依据。

Objective To explore the changes of pubescent immune response in the schizophrenia offspring induced by poly（I：C） during pregnancy and the effects on white matter. Methods The obtained pregnant rats were randomly divided into model group（ n= 6） and control group（ n= 5）, receiving either poly（ I： C） at a dose of 10 mg/kg diluted in 0.9% NaC1 solution or vehicle solution alone （sterile pyrogen-free 0.9% NaC1） on gestation day 9 （GD9）.Immunohistochemical technique （IHC） was applied to detect the changes of microglias and astrocytes in the prefrontal cortex（PFC） and hippocampus（HC） of partly offsprings in the two groups at the sixth week,as well as Luxol fast blue（LFB） for the changes of white matter. The other offsprings of each group were selected for behavioral assessment at the eighth week. Results The results of prepulse inhibition test showed that PP2, PP4 and P P8 of model groups were significantly lower than that of the control group at young adult （P〈0.01）. In passive avoidance test, and the T1 results of model group were significantly higher than those of the control group, the T results of model group were lower than those of control group （P〈 0.01 ）. Immunohistochemical results indicated that the number of microglias in the model group （ （ 264 ± 33 ）/mm2, （ 271 ± 38 ）/mm2 ） was significantly increased in PFC and HC than that in the control group（（140±29）/mm2, （169±37）/mm2, P〈0.05） ,which was accompanied with significant morphological changes, while the OD value of astrocyte protein expression in the frontal lobe and hippoeampus had no obvious difference between the model group and control group（P〉0.05 ）.The OD value of LFB staining for myelin in the model group（0.29±0.02） was significantly decreased compared with that in the control group（0.33±0.03）（P〈0.01 ）. Conclusion The young adult offsprings with prenatal infection present obvious schizophrenia-like behavior, meanwhile, the microglias activation and demyelination changes in white matter are observed, which provides more evidence for the relationship between immune response and white matter in the pathogenesis of schizophrenia.