Neuronal MAP kinase p38α inhibits c-Jun N-terminal kinase to modulate anxiety-related behaviour

Kristie Stefanoska, Josefine Bertz, Alexander M. Volkerling, Julia van der Hoven, Lars M. Ittner, Arne Ittner

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)

Abstract

Modulation of behavioural responses by neuronal signalling pathways remains incompletely understood. Signalling via mitogen-activated protein (MAP) kinase cascades regulates multiple neuronal functions. Here, we show that neuronal p38α, a MAP kinase of the p38 kinase family, has a critical and specific role in modulating anxiety-related behaviour in mice. Neuron-specific p38α-knockout mice show increased levels of anxiety in behaviour tests, yet no other behavioural, cognitive or motor deficits. Using CRISPR-mediated deletion of p38α in cells, we show that p38α inhibits c-Jun N-terminal kinase (JNK) activity, a function that is specific to p38α over other p38 kinases. Consistently, brains of neuron-specific p38α-knockout mice show increased JNK activity. Inhibiting JNK using a specific blood-brain barrier-permeable inhibitor reduces JNK activity in brains of p38α-knockout mice to physiological levels and reverts anxiety behaviour. Thus, our results suggest that neuronal p38α negatively regulates JNK activity that is required for specific modulation of anxiety-related behaviour.

Original languageEnglish
Article number14296
Number of pages12
JournalScientific Reports
Volume8
Early online date24 Sep 2018
DOIs
Publication statusPublished - 2018
Externally publishedYes

Keywords

  • Anxiety-related Behavior
  • Open-field Paradigm
  • Novel Object Recognition (NOR)
  • Elevated Plus-maze (EPM)
  • Neuronal Deletion
  • Kinases
  • Molecular neuroscience

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