Enhanced Survival of Wild-Type and Lurcher Purkinje Cells In Vitro Following Inhibition of Conventional PKCs or Stress-Activated MAP Kinase Pathways
Autor: | Ann M. Lohof, Hadi Shojaeian Zanjani, Michael W. Vogel, Rebecca McFarland, Jean Mariani |
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Přispěvatelé: | Développement, Réparation et Vieillissement Cérébral (DRVC), Adaptation Biologique et Vieillissement = Biological Adaptation and Ageing (B2A), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), NIH [NS 34309], ``Centre National de la Recherche Scientifique', Universite Pierre et Marie Curie, Laboratoire Internationaux Associe grant from UPMC, UPMC, Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS) |
Rok vydání: | 2012 |
Předmět: |
Male
Cell death Calbindins Programmed cell death Cell Survival [SDV]Life Sciences [q-bio] Lurcher Mice Transgenic Lurcher mutant mouse Biology Gene Expression Regulation Enzymologic Article Mice 03 medical and health sciences Organ Culture Techniques 0302 clinical medicine Cerebellum Animals Enzyme Inhibitors PKC Protein Kinase C Organotypic culture Protein kinase C 030304 developmental biology Analysis of Variance 0303 health sciences Caspase 3 Glutamate receptor Wild type Molecular biology Cell biology Animals Newborn Receptors Glutamate Neurology Purkinje cells Cell culture Mitogen-activated protein kinase Mice Inbred CBA biology.protein Calcium Female MAP kinase JNK Neurology (clinical) Mitogen-Activated Protein Kinases 030217 neurology & neurosurgery Intracellular Signal Transduction |
Zdroj: | The Cerebellum The Cerebellum, 2013, 12 (3), pp.377-389. ⟨10.1007/s12311-012-0427-x⟩ The Cerebellum, Springer, 2013, 12 (3), pp.377-389. ⟨10.1007/s12311-012-0427-x⟩ The Cerebellum, Taylor & Francis Ltd., 2013, 12 (3), pp.377-389. ⟨10.1007/s12311-012-0427-x⟩ |
ISSN: | 1473-4230 1473-4222 |
Popis: | International audience; Recent studies using both dissociated and organotypic cell cultures have shown that heterozygous Lurcher (Lc/+) Purkinje cells (PCs) grown in vitro share many of the same survival and morphological characteristics as Lc/+ PCs in vivo. We have used this established tissue culture system as a valuable model for studying cell death mechanisms in a relatively simple system where neurodegeneration is induced by a constitutive cation leak mediated by the Lurcher mutation in the delta 2 glutamate receptor (GluR delta 2). In this study, Ca++ imaging and immunocytochemistry studies indicate that intracellular levels of Ca++ are chronically increased in Lc/+ PCs and the concentration and/or distribution of the conventional PKC gamma isoform is altered in degenerating Lc/+ PCs. To begin to characterize the molecular mechanisms that regulate Lc/+ PC death, the contributions of conventional PKC pathways and of two MAP kinase family members, JNK and p38, were examined in slice cultures from wild-type and Lc/+ mutant mouse cerebellum. Cerebellar slice cultures from P0 pups were treated with either a conventional PKC inhibitor, a JNK inhibitor, or a p38 inhibitor either from 0 to 14 or 7 to 14 DIV. Treatment with either of the three inhibitors from 0 DIV significantly increased wild type and Lc/+ PC survival through 14 DIV, but only Lc/+ PC survival was significantly increased following treatments from 7 to 14 DIV. The results suggest that multiple PC death pathways are induced by the physical trauma of making organotypic slice cultures, naturally-occurring postnatal cell death, and the GluR delta 2 (Lc) mutation. |
Databáze: | OpenAIRE |
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