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

Takács, J. (2012) Unusual morphological damage of purkinje cells following postnatal BrdU administration in the cerebellar cortex of mouse. Acta Biologica Hungarica, 63 (Supple). pp. 19-37. ISSN 0236-5383

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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 results in more or less serious damage or death of 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 integration as well as partial loss of cerebellar Purkinje cells. In the present study, C57Bl6 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 were high at P9 and P11, especially in vermal lobules VIII, IX, and X. By P13 and P15 the number and 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.

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