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出生后给小鼠小脑皮质注射溴脱氧尿苷(BrdU)后浦肯野细胞出现异常形态损伤。

Unusual morphological damage of Purkinje cells following postnatal BrdU administration in the cerebellar cortex of mouse.

作者信息

Takács T

机构信息

Infibionic and Neurobiological Palsticity Research Group of the Hungarian Academy of Sciences, Péter Pázmány Catholic University, Semmelweis, Budapest, Hungary.

出版信息

Acta Biol Hung. 2012;63 Suppl 1:19-37. doi: 10.1556/ABiol.63.2012.Suppl.1.4.

DOI:10.1556/ABiol.63.2012.Suppl.1.4
PMID:22514871
Abstract

Postnatal development of the cerebellum lasts for weeks in rodents and can be disturbed by systemic 5-bromo-2'-deoxyuridine (BrdU) administration. This thymidine analogue incorporates into the DNA of proliferating cells, and result in more or less serious damage or death granule cells, the most actively dividing neuronal population in the developing cerebellar cortex. Further consequences of postnatal BrdU administration are the interrupted postnatal migration and integrations as well as partial loss of cerebellar Purkinje cells. In the present study, C57B16 mice were administered with 50 μg/g body weight BrdU, one sc. injection daily, between P0 and P11 postnatal days, respectively.Large "cavities" appeared in the cytoplasm of a subpopulation of Purkinje cells by P7 in about one-third of administered animals, their number are size of the cavities (and PCs exhibiting unusual morphology) decreased. EM studies revealed that the unusual Purkinje cells received numerous axonal inputs of unknown origin, first of all on their somatic and dendritic spines. The transitory appearance of a subpopulation of Purkinje cells possessing unusual morphology refers to the influence of other (neuronal, glial, or both) cells on their regular differentiation.

摘要

在啮齿动物中,小脑的产后发育持续数周,全身注射5-溴-2'-脱氧尿苷(BrdU)会干扰这一过程。这种胸腺嘧啶类似物会掺入增殖细胞的DNA中,或多或少地导致颗粒细胞严重受损或死亡,颗粒细胞是发育中小脑皮质中分裂最活跃的神经元群体。产后给予BrdU的进一步后果是产后迁移和整合中断,以及小脑浦肯野细胞部分丢失。在本研究中,分别在出生后第0天至第11天,给C57B16小鼠腹腔注射50μg/g体重的BrdU,每日一次。在约三分之一接受注射的动物中,到出生后第7天,浦肯野细胞亚群的细胞质中出现了大的“空洞”,空洞的数量及其大小(以及形态异常的浦肯野细胞数量)减少。电子显微镜研究表明,形态异常的浦肯野细胞接收了大量来源不明的轴突输入,首先是在它们的胞体和树突棘上。具有异常形态的浦肯野细胞亚群的短暂出现表明其他(神经元、胶质细胞或两者)细胞对其正常分化产生了影响。

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