Unknown

Dataset Information

0

Neuronal MAP kinase p38? inhibits c-Jun N-terminal kinase to modulate anxiety-related behaviour.


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

SUBMITTER: Stefanoska K 

PROVIDER: S-EPMC6155170 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

altmetric image

Publications

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

Stefanoska Kristie K   Bertz Josefine J   Volkerling Alexander M AM   van der Hoven Julia J   Ittner Lars M LM   Ittner Arne A  

Scientific reports 20180924 1


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.  ...[more]

Similar Datasets

| S-EPMC3628274 | biostudies-literature
| S-EPMC2568995 | biostudies-literature
| S-EPMC2825087 | biostudies-literature
| S-EPMC4344457 | biostudies-literature
| S-EPMC2223674 | biostudies-literature
| S-EPMC5356685 | biostudies-literature
| S-EPMC4030013 | biostudies-literature
| S-EPMC2967590 | biostudies-literature
| S-EPMC1805438 | biostudies-literature
| S-EPMC1221442 | biostudies-other