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Evolution of the Purkinje cell response to injury and regenerative potential during postnatal development of the rat cerebellum
Author(s) -
Gianola Sara,
Rossi Ferdinando
Publication year - 2000
Publication title -
journal of comparative neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.855
H-Index - 209
eISSN - 1096-9861
pISSN - 0021-9967
DOI - 10.1002/1096-9861(20010129)430:1<101::aid-cne1017>3.0.co;2-z
Subject(s) - axotomy , biology , purkinje cell , cerebellum , neuroscience , neurite , microbiology and biotechnology , central nervous system , biochemistry , in vitro
To understand the mechanisms leading to the progressive loss of intrinsic neuronal growth properties during central nervous system development, we have investigated the evolution of the response to injury and regenerative potential of immature Purkinje cells, axotomised at different postnatal ages from postnatal day (P)3 to P12. In adult rodents, these neurons are characterised by a weak cell body response to axotomy, which is associated with a remarkable resistance to injury and a poor regenerative capability. During the first postnatal week, Purkinje cells are strongly sensitive to injury and massively degenerate within a few days. Immature Purkinje cells react to neurite transection by a strong upregulation of c‐Jun, accompanied by a moderate, but consistent, expression of the growth‐associated protein (GAP)‐43. In contrast, nicotinamide adenine dinucleotide monophosphate (NADPH)‐diaphorase reactivity, which can be activated by adult Purkinje neurons, is not modified in their juvenile counterparts. The severed Purkinje axons show a vigorous regenerative sprouting both into the lesioned cerebellar environment and into embryonic neocortical tissue transplanted into the injury site. The typical adult features of the response to injury progressively develop during the second postnatal week, when the injured neurons acquire resistance, cell body changes become milder, the regenerative potential declines, and the severed axons undergo characteristic morphological modifications, including torpedoes and the hypertrophy of recurrent collateral branches. This complete reversal of the features and the outcome of the Purkinje cell reaction to axotomy likely results from the profound changes that occur in the maturing Purkinje cells and/or in their microenvironment during this phase of cerebellar development. J. Comp. Neurol. 430:101–117, 2001. © 2000 Wiley‐Liss, Inc.