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Role of GAP‐43 in mediating the responsiveness of cerebellar and precerebellar neurons to axotomy
Author(s) -
Wehrlé Rosine,
Caroni Pico,
Sotelo Constantino,
Dusart Isabelle
Publication year - 2001
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1046/j.1460-9568.2001.01452.x
Subject(s) - axotomy , biology , cerebellum , sprouting , neuroscience , purkinje cell , microbiology and biotechnology , deep cerebellar nuclei , anatomy , cerebellar cortex , central nervous system , botany
To determine whether the competence for axonal sprouting and/or regeneration in the cerebellar system correlates with GAP‐43 expression, we have studied GAP‐43 mRNA and protein expression in the postlesioned cerebellum and inferior olive. Purkinje cells transiently express GAP‐43 during their developmental phase (from E15 to P5 in the rat) which consists of fast axonal growth and the formation of the corticonuclear projection. Adult Purkinje cells, which in control adult rats do not express GAP‐43, are extremely resistant to the effects of axotomy but cannot regenerate axons. However, a late and protracted sprouting of axotomized Purkinje cells occurs spontaneously and correlates with a mild expression of GAP‐43 mRNA. In contrast, inferior olivary neurons, despite their high constitutive expression of GAP‐43, do not sprout but retract their axons and die after axotomy. Furthermore, mature Purkinje cells in cerebellar explants of transgenic mice that overexpress GAP‐43 do not regenerate after axotomy, even in the presence of a permissive substrate (cerebellar embryonic tissue) and, contrary to the case in wild‐type mice, they do not survive in the in vitro conditions and undergo massive cell death. These results show that the expression of GAP‐43 is not only associated with axonal growth, but also with neuronal death.