| First Author | Zhang Z | Year | 2017 |
| Journal | Neuroscience | Volume | 358 |
| Pages | 115-123 | PubMed ID | 28684277 |
| Mgi Jnum | J:249785 | Mgi Id | MGI:6092934 |
| Doi | 10.1016/j.neuroscience.2017.06.048 | Citation | Zhang Z, et al. (2017) NLRP3 inflammasome activation mediates fatigue-like behaviors in mice via neuroinflammation. Neuroscience 358:115-123 |
| abstractText | Numerous experimental and clinical studies have suggested that the interaction between the immune system and the brain plays an important role in the pathophysiology of chronic fatigue syndrome (CFS). The NLRP3 inflammasome is an important part of the innate immune system. This complex regulates proinflammatory cytokine interleukin-1beta (IL-1beta) maturation, which triggers different kinds of immune-inflammatory reactions. We employed repeated forced swims to establish a model of CFS in mice. NLRP3 knockout (KO) mice were also used to explore NLRP3 inflammasome activation in the mechanisms of CFS, using the same treatment. After completing repeated swim tests, the mice displayed fatigue-like behaviors, including locomotor activity and reduced fall-off time on the rota-rod test, which was accompanied by significantly higher mature IL-1beta level in the prefrontal cortex (PFC) and malondialdehyde (MDA) level in serum. We also found increased NLRP3 protein expression, NLRP3 inflammasome formation and increased mature IL-1beta production in the PFC, relative to untreated mice. The NLRP3 KO mice displayed significantly moderated fatigue behaviors along with decreased PFC and serum IL-1beta levels under the same treatment. These findings demonstrated the involvement of NLRP3 inflammasome activation in the mechanism of swimming-induced fatigue. Future therapies targeting the NLRP3/IL-1beta pathway may have significant potential for fatigue prevention and treatment. |
