QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (35) Citing Articles via Google Scholar Google Scholar Articles by Ghoumari, A. M. Articles by Dusart, I. Search for Related Content PubMed PubMed Citation Articles by Ghoumari, A. M. Articles by Dusart, I. Pubmed/NCBI databases Compound via MeSH Substance via MeSH

 Previous Article  |  Next Article 

The Journal of Neuroscience, May 1, 2002, 22(9):3531-3542

Inhibition of Protein Kinase C Prevents Purkinje Cell Death But Does Not Affect Axonal Regeneration

Abdel M. Ghoumari¹, Rosine Wehrlé¹, Chris I. De Zeeuw², Constantino Sotelo¹, and Isabelle Dusart¹

¹ Institut National de la Santé et de la Recherche Médicale Unité 106, Hôpital de la Salpêtrière, 75651 Paris Cedex 13, France, and ² Department of Anatomy, Neuroscience Institute, Faculteit der Geneeskunde en Gezondheidswetenschappen, Erasmus, University Rotterdam, 3000 DR Rotterdam, The Netherlands

In organotypic cultures, mouse Purkinje cells regenerate their axons from embryonic day 18 (E18) to postnatal day 0 (P0), die of apoptosis between P1 and P7, and survive but do not regenerate at P10. This particular behavior of Purkinje cells did not allow us to find out when the developmental switch between regeneration and lack of regeneration occurs. This work was undertaken to suppress Purkinje cell apoptosis and to investigate whether the same molecules that prevent apoptosis could also influence axonal growth, regeneration, or both. We show that brain-derived neurotrophic factor, neurotrophin 3, and insulin-like growth factor I have marginal effects on P3 Purkinje cell death. The use of Gö6976 [a protein kinase C (PKC) inhibitor] or a transgenic mouse line, in which a pseudosubstrate PKC inhibitor has been specifically targeted to Purkinje cells, prevents the massive Purkinje cell death in P3 organotypic cultures. In addition, Gö6976 promotes axotomized Purkinje cell survival up to P7. Thus, the inhibition of PKC activity is able to prevent Purkinje cell apoptosis in organotypic cultures. Furthermore, Gö6976 increases the outgrowth of dendrites and axon collateralization, as shown after gene gun enhanced green fluorescent protein transfection. In contrast, PKC inhibitors do not influence the axonal regenerative capability of Purkinje cell during development; the latter decreases between E18 and P7 after the same time course in control and Gö6976-treated slices. Thus, because inhibition of PKC prevents Purkinje cell death but does not affect axonal regeneration, these two events (cell death and axonal regeneration) seem to be differentially regulated.

Key words: axotomy; apoptosis; trophic factor; cerebellum; PKC inhibitor; development

---

Copyright © 2002 Society for Neuroscience  0270-6474/02/2293531-12$05.00/0

This article has been cited by other articles:

				M. Schumacher, R. Guennoun, A. Ghoumari, C. Massaad, F. Robert, M. El-Etr, Y. Akwa, K. Rajkowski, and E.-E. Baulieu Novel Perspectives for Progesterone in Hormone Replacement Therapy, with Special Reference to the Nervous System Endocr. Rev., June 1, 2007; 28(4): 387 - 439. [Abstract] [Full Text] [PDF]

				R. R. Kimpo and J. L. Raymond Impaired Motor Learning in the Vestibulo-Ocular Reflex in Mice with Multiple Climbing Fiber Input to Cerebellar Purkinje Cells J. Neurosci., May 23, 2007; 27(21): 5672 - 5682. [Abstract] [Full Text] [PDF]

				J. Li, J. Imitola, E. Y. Snyder, and R. L. Sidman Neural stem cells rescue nervous purkinje neurons by restoring molecular homeostasis of tissue plasminogen activator and downstream targets. J. Neurosci., July 26, 2006; 26(30): 7839 - 7848. [Abstract] [Full Text] [PDF]

				A. M. Ghoumari, C. Piochon, C. Tomkiewicz, B. Eychenne, C. Levenes, I. Dusart, M. Schumacher, and E. E. Baulieu Neuroprotective effect of mifepristone involves neuron depolarization FASEB J, July 1, 2006; 20(9): 1377 - 1386. [Abstract] [Full Text] [PDF]

				K. Lister, D. J. Autelitano, A. Jenkins, R. D. Hannan, and K. E. Sheppard Cross talk between corticosteroids and alpha-adrenergic signalling augments cardiomyocyte hypertrophy: A possible role for SGK1 Cardiovasc Res, June 1, 2006; 70(3): 555 - 565. [Abstract] [Full Text] [PDF]

				J. Li, Y. Ma, Y. D. Teng, K. Zheng, T. K. Vartanian, E. Y. Snyder, and R. L. Sidman Purkinje neuron degeneration in nervous (nr) mutant mice is mediated by a metabolic pathway involving excess tissue plasminogen activator PNAS, May 16, 2006; 103(20): 7847 - 7852. [Abstract] [Full Text] [PDF]

				F. Boukhtouche, S. Janmaat, G. Vodjdani, V. Gautheron, J. Mallet, I. Dusart, and J. Mariani Retinoid-Related Orphan Receptor {alpha} Controls the Early Steps of Purkinje Cell Dendritic Differentiation J. Neurosci., February 1, 2006; 26(5): 1531 - 1538. [Abstract] [Full Text] [PDF]

				D. S. Verbeek, M. A. Knight, G. G. Harmison, K. H. Fischbeck, and B. W. Howell Protein kinase C gamma mutations in spinocerebellar ataxia 14 increase kinase activity and alter membrane targeting Brain, February 1, 2005; 128(2): 436 - 442. [Abstract] [Full Text] [PDF]

				L. Bouslama-Oueghlani, R. Wehrle, C. Sotelo, and I. Dusart The Developmental Loss of the Ability of Purkinje Cells to Regenerate Their Axons Occurs in the Absence of Myelin: An In Vitro Model to Prevent Myelination J. Neurosci., September 10, 2003; 23(23): 8318 - 8329. [Abstract] [Full Text] [PDF]

				A. M. Ghoumari, I. Dusart, M. El-Etr, F. Tronche, C. Sotelo, M. Schumacher, and E.-E. Baulieu Mifepristone (RU486) protects Purkinje cells from cell death in organotypic slice cultures of postnatal rat and mouse cerebellum PNAS, June 24, 2003; 100(13): 7953 - 7958. [Abstract] [Full Text] [PDF]

				S. Gianola, T. Savio, M. E. Schwab, and F. Rossi Cell-Autonomous Mechanisms and Myelin-Associated Factors Contribute to the Development of Purkinje Axon Intracortical Plexus in the Rat Cerebellum J. Neurosci., June 1, 2003; 23(11): 4613 - 4624. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help