Loss of NF-κB p50 function synergistically augments microglial priming in the middle-aged brain View Full Text


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Article Info

DATE

2019-12

AUTHORS

Thomas Taetzsch, Savannah Benusa, Shannon Levesque, Christen L. Mumaw, Michelle L. Block

ABSTRACT

BACKGROUND: While NF-κB p50 function is impaired in central nervous system disease, aging in non-CNS tissues, and response to reactive oxygen species, the role of NF-κB p50 in aging-associated microglial pro-inflammatory priming is poorly understood. METHODS: Male NF-κB p50+/+ and NF-κB 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-κB 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-κB 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-κB p50 activity in the brain across the mouse lifespan. To examine the consequences of loss NF-κB p50 function with aging, NF-κB p50+/+ and NF-κB 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-κB p50-/- mice showed markedly elevated circulating, midbrain, and microglial TNFα when compared to NF-κB p50+/+ mice at all ages. Notably, the 16.0-18.0-month-old (middle aged) NF-κB p50-/- mice exhibited synergistically augmented LPS-induced serum and midbrain TNFα when compared to the younger (1.5-3.0 month old, young adult) NF-κB p50-/- mice. The 16.0-18.0-month-old LPS-treated NF-κB p50-/- mice also had the highest midbrain IL-1β expression, largest number of microglia with changes in morphology, and greatest elevation of pro-inflammatory factors in isolated adult microglia. Interestingly, aging NF-κB p50-/- mice exhibited decreased brain NF-κB p65 expression and activity. CONCLUSIONS: These findings support that loss of NF-κB 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-κB p50/p65 transcription factor in this process. More... »

PAGES

60

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/s12974-019-1446-z

DOI

http://dx.doi.org/10.1186/s12974-019-1446-z

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1112765366

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30871598


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Download the RDF metadata as:  json-ld nt turtle xml License info

HOW TO GET THIS DATA PROGRAMMATICALLY:

JSON-LD is a popular format for linked data which is fully compatible with JSON.

curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1186/s12974-019-1446-z'

N-Triples is a line-based linked data format ideal for batch operations.

curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1186/s12974-019-1446-z'

Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1186/s12974-019-1446-z'

RDF/XML is a standard XML format for linked data.

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1186/s12974-019-1446-z'


 

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