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Specific JNK Inhibition by D-JNKI1 Protects Purkinje Cells from Cell Death in Lurcher Mutant Mouse

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Abstract

In the Lurcher mutant mouse (+/Lc), Purkinje cells (PCs) selectively die due to the mutation that converts alanine to threonine in the glutamate ionotropic receptor GRID 2, thus resulting in a constitutively leaky cation channel. This intrinsic cell death determines a target-dependent cell death of granule cells and olivary neurons and cerebellum cytoarchitecture is severely disrupted in the adult Lurcher mutant. Although the +/Lc mutant has been widely characterized, less is known about the molecules involved in +/Lc PC death. We, here, used organotypic cerebellar slice cultures from P0 mice to investigate the role of c-jun N-terminal kinase (JNK) in +/Lc PC death by using D-JNKI1 as very specific tool to inhibit its action. Our results showed that D-JNKI1 treatment increased the number of +/Lc PC at 14 DIV of 3.6-fold. Conversely, this specific JNK inhibitor cell permeable peptide did not increase PC number in +/+ treated versus untreated cultures. These results clearly indicate that JNK plays an important role in +/Lc PC mechanism of cell death.

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Acknowledgments

Dr. Repici was supported by an FRM grant. D-JNKI1 peptide was kindly provided by Xigen, SA, Rue des Terreaux 17, CH-1003 Lausanne, Switzerland. We thank Dr. Rudolf Kraftsik for statistical analysis.

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Authors and Affiliations

  1. Centre National de la Recherche Scientifique (CNRS), UMR7102-Neurobiologie des Processus Adaptatifs (NPA), Paris, F-75005, France

    Mariaelena Repici, Hadi S. Zanjani, Vanessa Gautheron, Isabelle Dusart & Jean Mariani

  2. UPMC Univ Paris 06, UMR 7102, NPA, Bat B, 6eme, Case 12, 9 Quai Saint Bernard, 75005, Paris, France

    Mariaelena Repici, Hadi S. Zanjani, Vanessa Gautheron, Isabelle Dusart & Jean Mariani

  3. Istituto di Ricerche Farmacologiche “Mario Negri”, Via la Masa 19, 20156, Milan, Italy

    Tiziana Borsello

  4. Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, P.O. Box 21247, Baltimore, MD, 21228, USA

    Hadi S. Zanjani

  5. AP-HP, Hôpital Charles Foix, UEF, Ivry sur Seine, F-94-200, France

    Jean Mariani

Authors
  1. Mariaelena Repici
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  2. Hadi S. Zanjani
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  3. Vanessa Gautheron
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  4. Tiziana Borsello
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  5. Isabelle Dusart
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  6. Jean Mariani
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Correspondence to Isabelle Dusart.

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Repici, M., Zanjani, H.S., Gautheron, V. et al. Specific JNK Inhibition by D-JNKI1 Protects Purkinje Cells from Cell Death in Lurcher Mutant Mouse. Cerebellum 7, 534–538 (2008). https://doi.org/10.1007/s12311-008-0070-8

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  • DOI: https://doi.org/10.1007/s12311-008-0070-8

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