Cell death and axon regeneration of Purkinje cells after axotomy: challenges of classical hypotheses of axon regeneration.
Although adult mammalian neurons are able to regenerate their axons in the peripheral nervous system under certain conditions, they are not able to do it in the central nervous system. The environment surrounding the severed axons appears to be a key factor for axon regeneration. Many studies aiming to enhance axon regeneration in the CNS of adult mammals have successfully manipulated this environment by adding growth permissive molecules and/or neutralizing growth inhibitory molecules. In both cases, the number of axons able to regenerate was low and the different neuronal populations were not equal in their regenerative response, suggesting that manipulation of the environment is not always sufficient. This is particularly well illustrated in the cerebellar system, in which axotomized inferior olivary neurons regenerate when confronted with a permissive environment, whereas mature Purkinje cells do not. The intrinsic ability of a neuron to regenerate its axon is generally correlated with the intensity of its reaction to axotomy (expression of molecules, probability to die). Furthermore, molecules such as GAP-43 (growth-associated molecule) and c-Jun are involved in both axon regeneration and cell death suggesting that these two processes are linked. Surprisingly, Purkinje cells lose their capacity to regenerate their axon (even in the absence of myelin) during development before losing their capacity to react to an axotomy by cell death. These results emphasize the different reactions to axotomy between neuron types and underline that in Purkinje cells, the two cell decisions (axon regeneration and cell death) are differently regulated and therefore not part of the same signaling pathway.
Dusart
I
I
UMR-7102, Université Pierre et Marie Curie, 9 Quai Saint Bernard, 75005 Paris, France. isabelle.dusart@snv.jussieu.fr
Ghoumari
A
A
Wehrle
R
R
Morel
M P
MP
Bouslama-Oueghlani
L
L
Camand
E
E
Sotelo
C
C
D000818:Animals; D001369:Axons / Q000473:pathology / Q000502:physiology*; D019771:Axotomy; D016923:Cell Death / Q000502:physiology; D008959:Models, Neurological; D009416:Nerve Regeneration / Q000502:physiology*; D011689:Purkinje Cells / Q000473:pathology* / Q000502:physiology