Proliferation and migration of granule cells in the developing rat cerebellum: Cisplatin effects

Abstract

We evaluated the relationship among proliferation, death and migration of granule cells in lobules VI-VIII of vermis, in comparison with lobule III, during cerebellar development. To this aim, a single injection of cisplatin, i.e., a cytostatic agent that is known to induce death of proliferating granule cells, was given to 10-day-old rats. Histochemical markers of proliferating (PCNA immunoreaction) and apoptotic (TUNEL staining) cells were used; the variations of the external granular layer (EGL) thickness were evaluated in parallel. After PCNA and TUNEL reactions, evident changes of the whole EGL were found on PD11 (1 day after treatment), when a reduction of the thickness of this layer was found in treated rats, mainly in consequence of the high number of apoptotic cells in all the cerebellar lobules. On PD17 (7 days after treatment), a thick layer of proliferating cells was observed in lobules VI-VIII of treated rats, while the peculiar pattern of the normal development showed a thin EGL. At the same time, in treated rats, the number of apoptotic cells in EGL was low. In all developmental stages of treated rats, after GFAP immunoreaction, glial fibers appeared twisted, thickened, and with an irregular course; intensely labeled end-feet were present. The damage of radial glia suggests an alteration of migratory processes of granule cells, which is also evidenced by the decreased thickness of the premigratory zone of the EGL. Injured radial glia fibers were restricted to lobules VI-VIII and they persisted at PD30, leading to the presence of ectopic granule cells in the molecular layer, as we previously described.

Tomato pomace powder ameliorated cisplatin-induced microanatomical alterations in brain of Wistar rats

“…Similarly, cisplatin also caused complete dissolution of the basophilic materials of the nuclei of Purkinje cells of the cerebellum of the rats showing eosinophilia. This agrees with the report of Pisu et al (2004Pisu et al ( , 2005) that cisplatin has negative effects on cerebellar cortex neurons, especially Purkinje cells. Although platinum drugs are reported to have poor penetration of the blood-brain barrier (Gregg et al, 1992), sufficient levels of cisplatin have been shown to cause toxicity in the brain (Gulec et al, 2013), which this study demonstrated.…”

Intrauterine Growth Restriction Alters the Postnatal Development of the Rat Cerebellum

“…This concept is supported by the finding that Ric-8a null mice with disrupted Bergmann glial fibers also showed deficits in granule cell migration [43,44] . Our data suggest that altered development of the Bergmann glial fibers with IUGR may impact the migration of the granule cells.…”

Postnatal Development of the Central Nervous System: Anomalies in the Formation of Cerebellum Fissures

“…In this light, we propose that the abnormal development of Purkinje cell dendrites detected at PD10 and PD11 is likely due to a changed guiding influence of parallel fibers as already observed by Altman (1973) as also may occur after cytotoxic injury (Pisu et al, 2004(Pisu et al, , 2005. Changes in this relationship may result in the disturbed cerebellar cytoarchitecture.…”

“…We evaluated the pattern/interaction of these cell populations in the following critical developmental stages: at postnatal day 10 (PD 10) and PD 11, when the first sign of malformation begins (Necchi et al, 2000) and active granule cell proliferation occurs (Altman, 1972a;Altman, 1982;Pisu et al, 2005), at PD 17, when granule cell proliferation and migration decline (Altman, 1972a(Altman, , 1982Pisu et al, 2005) and PD 30, i.e., after the end of histogenetic processes (Altman, 1982) in the rat.…”