Proliferation and migration of granule cells in the developing rat cerebellum: Cisplatin effects
Article first published online: 24 OCT 2005
Copyright © 2005 Wiley-Liss, Inc.
The Anatomical Record Part A: Discoveries in Molecular, Cellular, and Evolutionary Biology
Volume 287A, Issue 2, pages 1226–1235, December 2005
How to Cite
Pisu, M. B., Roda, E., Guioli, S., Avella, D., Bottone, M. G. and Bernocchi, G. (2005), Proliferation and migration of granule cells in the developing rat cerebellum: Cisplatin effects. Anat. Rec., 287A: 1226–1235. doi: 10.1002/ar.a.20249
- Issue published online: 24 NOV 2005
- Article first published online: 24 OCT 2005
- Manuscript Accepted: 18 JUL 2005
- Manuscript Received: 3 MAY 2005
- MIUR. Grant Number: COFIN 2002 (2002053351)
- Fondo Ateneo Ricerca
- cytostatic drug
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. © 2005 Wiley-Liss, Inc.