The α2­Na+ /K+ ‐ATPase isoform mediates LPS‐induced neuroinfammation

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The astrocyte-enriched α2-Na+/K+-ATPase is an integral plasma membrane protein responsible for maintaining Na+ and K+ gradients across cellular membranes supporting vital cellular functions. Missense mutations in the α2-isoform cause a subtype of migraine with aura. Additionally, loss-of-function of the α2-Na+/K+-ATPase is associated with the reduction of inflammatory response and neurodegeneration, however, the mechanisms for this are unclear. Here we show that mice heterozygous for the α2-isoform (α2+/G301R) exert a reduced systemic production of proinflammatory cytokines induced by LPS. In addition, LPS injection reduced the synthesis of TNF-α, IL-1β, and IL-6 in the hypothalamus and hippocampus, accompanied by a distinct hypothermic reaction. Moreover, α2+/G301R mice increase antioxidant enzyme expression in the hippocampus. Our results show that α2-Na+/K+-ATPase haploinsufficiency negatively modulates LPS-induced activation of the innate immune system and that the Na+/K+ is a critical component of the immune system. These data advance our understanding of how the α2-Na+/K+-ATPase isoform regulates inflammation and promote cytokines during neuroinflammation.
J. A. Leite, T. J. Isaksen, A. Heuck, C. Scavone & K. Lykke-Hartmann
Scientific Reports volume 10, Article number: 14180 (2020)