| First Author | Colié S | Year | 2017 |
| Journal | Sci Rep | Volume | 7 |
| Pages | 45306 | PubMed ID | 28361984 |
| Mgi Jnum | J:272779 | Mgi Id | MGI:6282380 |
| Doi | 10.1038/srep45306 | Citation | Colie S, et al. (2017) Neuronal p38alpha mediates synaptic and cognitive dysfunction in an Alzheimer's mouse model by controlling beta-amyloid production. Sci Rep 7:45306 |
| abstractText | Alzheimer's disease (AD) is a neurodegenerative disorder characterized by a severe and progressive neuronal loss leading to cognitive dysfunctions. Previous reports, based on the use of chemical inhibitors, have connected the stress kinase p38alpha to neuroinflammation, neuronal death and synaptic dysfunction. To explore the specific role of neuronal p38alpha signalling in the appearance of pathological symptoms, we have generated mice that combine expression of the 5XFAD transgenes to induce AD symptoms with the downregulation of p38alpha only in neurons (5XFAD/p38alpha-N). We found that the neuronal-specific deletion of p38alpha improves the memory loss and long-term potentiation impairment induced by 5XFAD transgenes. Furthermore, 5XFAD/p38alpha-N mice display reduced amyloid-beta accumulation, improved neurogenesis, and important changes in brain cytokine expression compared with 5XFAD mice. Our results implicate neuronal p38alpha signalling in the synaptic plasticity dysfunction and memory impairment observed in 5XFAD mice, by regulating both amyloid-beta deposition in the brain and the relay of this accumulation to mount an inflammatory response, which leads to the cognitive deficits. |
