c-Jun N-terminal kinase (JNK) and p38 play different roles in age-related Purkinje cell death in murine organotypic culture

Mariaelena Repici, Rosine Wehrlé, Xanthi Antoniou, Tiziana Borsello, Isabelle Dusart

Research output: Contribution to journalArticle

Abstract

Several studies have shown that Purkinje cells die by apoptosis in organotypic slice cultures from postnatal 3-day-old (P3) mice. This cell death is age-dependent and has been proposed as indirect evidence for the programmed Purkinje cell death occurring in in vivo cerebellum. Here, we studied whether c-jun N-terminal kinase (JNK) and p38 kinase pathways contribute to the Purkinje cell death observed in cerebellar slice cultures obtained from P3 mice. Slice culture treatment with D-JNKI1 or SB203580, respectively inhibitors of JNK and p38 MAP kinases, results in a better survival of Purkinje cells. Interestingly, the combined treatment with the two inhibitors potentiated single treatment effects. These results suggest that p38 and JNK pathways might be differently implicated in this Purkinje cell death. Time course experiments found p38 activation immediately post-slicing, whereas JNK activation was detected only 2 h after the culture. We hypothesize that p38 activation might be due to the "sliced condition," and JNK activation might be more specific to P3 age-dependent cell death. The study of JNK and p38 activation in cerebellar lysates from P0 slice culture confirmed JNK activation being specific for the P3 explants, whereas p38 is activated both from P0 and P3 cerebellar slice culture lysates. These results suggest that p38 is activated by the slicing, whereas JNK activation is related to developmental Purkinje cell death.

Original languageEnglish
Pages (from-to)281-290
Number of pages10
JournalThe Cerebellum
Volume10
Issue number2
DOIs
Publication statusPublished - Jun 2011

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JNK Mitogen-Activated Protein Kinases
Purkinje Cells
Cell Death
MAP Kinase Signaling System
Mitogen-Activated Protein Kinase Kinases
p38 Mitogen-Activated Protein Kinases
Cerebellum
Apoptosis

Keywords

  • Aging/physiology
  • Animals
  • Apoptosis/physiology
  • Artifacts
  • Blotting, Western
  • Enzyme Activation
  • JNK Mitogen-Activated Protein Kinases/metabolism
  • Mice
  • Organ Culture Techniques
  • Purkinje Cells/cytology
  • Specimen Handling/adverse effects
  • p38 Mitogen-Activated Protein Kinases/metabolism

Cite this

Repici, Mariaelena ; Wehrlé, Rosine ; Antoniou, Xanthi ; Borsello, Tiziana ; Dusart, Isabelle. / c-Jun N-terminal kinase (JNK) and p38 play different roles in age-related Purkinje cell death in murine organotypic culture. In: The Cerebellum. 2011 ; Vol. 10, No. 2. pp. 281-290.
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c-Jun N-terminal kinase (JNK) and p38 play different roles in age-related Purkinje cell death in murine organotypic culture. / Repici, Mariaelena; Wehrlé, Rosine; Antoniou, Xanthi; Borsello, Tiziana; Dusart, Isabelle.

In: The Cerebellum, Vol. 10, No. 2, 06.2011, p. 281-290.

Research output: Contribution to journalArticle

TY - JOUR

T1 - c-Jun N-terminal kinase (JNK) and p38 play different roles in age-related Purkinje cell death in murine organotypic culture

AU - Repici, Mariaelena

AU - Wehrlé, Rosine

AU - Antoniou, Xanthi

AU - Borsello, Tiziana

AU - Dusart, Isabelle

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N2 - Several studies have shown that Purkinje cells die by apoptosis in organotypic slice cultures from postnatal 3-day-old (P3) mice. This cell death is age-dependent and has been proposed as indirect evidence for the programmed Purkinje cell death occurring in in vivo cerebellum. Here, we studied whether c-jun N-terminal kinase (JNK) and p38 kinase pathways contribute to the Purkinje cell death observed in cerebellar slice cultures obtained from P3 mice. Slice culture treatment with D-JNKI1 or SB203580, respectively inhibitors of JNK and p38 MAP kinases, results in a better survival of Purkinje cells. Interestingly, the combined treatment with the two inhibitors potentiated single treatment effects. These results suggest that p38 and JNK pathways might be differently implicated in this Purkinje cell death. Time course experiments found p38 activation immediately post-slicing, whereas JNK activation was detected only 2 h after the culture. We hypothesize that p38 activation might be due to the "sliced condition," and JNK activation might be more specific to P3 age-dependent cell death. The study of JNK and p38 activation in cerebellar lysates from P0 slice culture confirmed JNK activation being specific for the P3 explants, whereas p38 is activated both from P0 and P3 cerebellar slice culture lysates. These results suggest that p38 is activated by the slicing, whereas JNK activation is related to developmental Purkinje cell death.

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KW - Animals

KW - Apoptosis/physiology

KW - Artifacts

KW - Blotting, Western

KW - Enzyme Activation

KW - JNK Mitogen-Activated Protein Kinases/metabolism

KW - Mice

KW - Organ Culture Techniques

KW - Purkinje Cells/cytology

KW - Specimen Handling/adverse effects

KW - p38 Mitogen-Activated Protein Kinases/metabolism

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DO - 10.1007/s12311-010-0244-z

M3 - Article

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VL - 10

SP - 281

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JO - The Cerebellum

JF - The Cerebellum

SN - 1473-4222

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ER -