In vivo analysis reveals different apoptotic pathways in pre‐ and postmigratory cerebellar granule cells of rabbit

Naturally occurring neuronal death (NOND) has been described in the postnatal cerebellum of several species, mainly affecting the cerebellar granule cells (CGCs) by an apoptotic mechanism. However, little is known about the cellular pathway(s) of CGC apoptosis in vivo. By immunocytochemistry, in sit...

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Bibliographic Details
Published in:Journal of neurobiology 2004-09, Vol.60 (4), p.437-452
Main Authors: Lossi, Laura, Gambino, Graziana, Mioletti, Silvia, Merighi, Adalberto
Format: Article
Language:English
Subjects:
Animals
apoptosis
Apoptosis - genetics
Apoptosis - physiology
Caspase 3
Caspases - metabolism
cell cycle
Cell Cycle - genetics
Cell Differentiation - genetics
Cell Movement - genetics
Cerebellar Cortex - growth & development
Cerebellar Cortex - metabolism
Cerebellar Cortex - ultrastructure
cerebellum
checkpoint kinase
Checkpoint Kinase 1
Genes, cdc - physiology
Immunohistochemistry
Microscopy, Electron, Transmission
Neurons - metabolism
Neurons - ultrastructure
Phosphorylation
programmed cell death
Protein Kinases - metabolism
Proteins - metabolism
Rabbits
retinoblastoma protein
Retinoblastoma Protein - metabolism
Signal Transduction - physiology
Stem Cells - cytology
Stem Cells - metabolism
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Summary:Naturally occurring neuronal death (NOND) has been described in the postnatal cerebellum of several species, mainly affecting the cerebellar granule cells (CGCs) by an apoptotic mechanism. However, little is known about the cellular pathway(s) of CGC apoptosis in vivo. By immunocytochemistry, in situ detection of fragmented DNA, electron microscopy, and Western blotting, we demonstrate here the existence of two different molecular mechanisms of apoptosis in the rabbit postnatal cerebellum. These two mechanisms affect CGCs at different stages of their maturation and migration. In the external granular layer, premigratory CGCs undergo apoptosis upon phosphorylation of checkpoint kinase 1 (Chk1), and hyperphosphorylation of retinoblastoma protein. In postmigratory CGCs within the internal granular layer, caspase 3 and to a lesser extent 7 and 9 are activated, eventually leading to poly‐ADP‐ribose polymerase‐1 (PARP‐1) cleavage and programmed cell death. We conclude that NOND of premigratory CGCs is linked to activation of DNA checkpoint and alteration of normal cell cycle, whereas in postmigratory CGCs apoptosis is, more classically, dependent upon caspase 3 activation. © 2004 Wiley Periodicals, Inc. J Neurobiol 60: 437–452, 2004
ISSN:0022-3034
1097-4695
DOI:10.1002/neu.20032