| First Author | Stefanoska K | Year | 2018 |
| Journal | Sci Rep | Volume | 8 |
| Issue | 1 | Pages | 14296 |
| PubMed ID | 30250211 | Mgi Jnum | J:278551 |
| Mgi Id | MGI:6356263 | Doi | 10.1038/s41598-018-32592-y |
| Citation | Stefanoska K, et al. (2018) Neuronal MAP kinase p38alpha inhibits c-Jun N-terminal kinase to modulate anxiety-related behaviour. Sci Rep 8(1):14296 |
| abstractText | 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 p38alpha, a MAP kinase of the p38 kinase family, has a critical and specific role in modulating anxiety-related behaviour in mice. Neuron-specific p38alpha-knockout mice show increased levels of anxiety in behaviour tests, yet no other behavioural, cognitive or motor deficits. Using CRISPR-mediated deletion of p38alpha in cells, we show that p38alpha inhibits c-Jun N-terminal kinase (JNK) activity, a function that is specific to p38alpha over other p38 kinases. Consistently, brains of neuron-specific p38alpha-knockout mice show increased JNK activity. Inhibiting JNK using a specific blood-brain barrier-permeable inhibitor reduces JNK activity in brains of p38alpha-knockout mice to physiological levels and reverts anxiety behaviour. Thus, our results suggest that neuronal p38alpha negatively regulates JNK activity that is required for specific modulation of anxiety-related behaviour. |
