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- W2892373731 abstract "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." @default.
- W2892373731 created "2018-09-27" @default.
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- W2892373731 date "2018-09-24" @default.
- W2892373731 modified "2023-10-12" @default.
- W2892373731 title "Neuronal MAP kinase p38α inhibits c-Jun N-terminal kinase to modulate anxiety-related behaviour" @default.
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- W2892373731 doi "https://doi.org/10.1038/s41598-018-32592-y" @default.
- W2892373731 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6155170" @default.
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