| First Author | Taetzsch T | Year | 2019 |
| Journal | J Neuroinflammation | Volume | 16 |
| Issue | 1 | Pages | 60 |
| PubMed ID | 30871598 | Mgi Jnum | J:291692 |
| Mgi Id | MGI:6445401 | Doi | 10.1186/s12974-019-1446-z |
| Citation | Taetzsch T, et al. (2019) Loss of NF-kappaB p50 function synergistically augments microglial priming in the middle-aged brain. J Neuroinflammation 16(1):60 |
| abstractText | BACKGROUND: While NF-kappaB p50 function is impaired in central nervous system disease, aging in non-CNS tissues, and response to reactive oxygen species, the role of NF-kappaB p50 in aging-associated microglial pro-inflammatory priming is poorly understood. METHODS: Male NF-kappaB p50(+/+) and NF-kappaB p50(-/-) mice at three different ages (1.5-3.0 month old, 8.0-11.0 month old, and 16.0-18.0 month old) were treated with LPS (5 mg/kg, IP) to trigger peripheral inflammation, where circulating cytokines, neuroinflammation, microglia morphology, and NF-kappaB p50/p65 function in brain tissue were determined 3 h later. RESULTS: Peripheral LPS injection in 9-month-old C57BL/6 mice resulted in lower NF-kappaB p50 DNA binding of nuclear extracts from the whole brain, when compared to 3-week-old C57BL/6 mice, revealing differences in LPS-induced NF-kappaB p50 activity in the brain across the mouse lifespan. To examine the consequences of loss NF-kappaB p50 function with aging, NF-kappaB p50(+/+) and NF-kappaB p50(-/-) mice of three different age groups (1.5-3.0 month old, 8.0-11.0 month old, and 16.0-18.0 month old) were injected with LPS (5 mg/kg, IP). NF-kappaB p50(-/-) mice showed markedly elevated circulating, midbrain, and microglial TNFalpha when compared to NF-kappaB p50(+/+) mice at all ages. Notably, the 16.0-18.0-month-old (middle aged) NF-kappaB p50(-/-) mice exhibited synergistically augmented LPS-induced serum and midbrain TNFalpha when compared to the younger (1.5-3.0 month old, young adult) NF-kappaB p50(-/-) mice. The 16.0-18.0-month-old LPS-treated NF-kappaB p50(-/-) mice also had the highest midbrain IL-1beta expression, largest number of microglia with changes in morphology, and greatest elevation of pro-inflammatory factors in isolated adult microglia. Interestingly, aging NF-kappaB p50(-/-) mice exhibited decreased brain NF-kappaB p65 expression and activity. CONCLUSIONS: These findings support that loss of NF-kappaB p50 function and aging in middle-aged mice may interact to excessively augment peripheral/microglial pro-inflammatory responses and point to a novel neuroinflammation signaling mechanism independent the NF-kappaB p50/p65 transcription factor in this process. |
