CX3CR1-microglia mediates neuroinflammation and blood pressure regulation in the nucleus tractus solitarii of fructose-induced hypertensive rats

Chiu Yi Ho, Chiu Yi Ho, Yu Te Lin, Yu Te Lin, Yu Te Lin, Yu Te Lin, Hsin Hung Chen, Wen Yu Ho, Wen Yu Ho, Gwo Ching Sun, Gwo Ching Sun, Michael Hsiao, Pei Jung Lu, Pei Wen Cheng, Pei Wen Cheng, Ching Jiunn Tseng, Ching Jiunn Tseng, Ching Jiunn Tseng

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Abstract

Background: Inflammation is a common pathophysiological trait found in both hypertension and cardiac vascular disease. Recent evidence indicates that fractalkine (FKN) and its receptor CX3CR1 have been linked to inflammatory response in the brain of hypertensive animal models. Here, we investigated the role of CX3CR1-microglia in nitric oxide (NO) generation during chronic inflammation and systemic blood pressure recovery in the nucleus tractus solitarii (NTS). Methods: The hypertensive rat model was used to study the role of CX3CR1-microglia in NTS inflammation following hypertension induction by oral administration of 10% fructose water. The systolic blood pressure was measured by tail-cuff method of non-invasive blood pressure. The CX3CR1 inhibitor AZD8797 was administered intracerebroventricularly (ICV) in the fructose-induced hypertensive rat. Using immunoblotting, we studied the nitric oxide synthase signaling pathway, NO concentration, and the levels of FKN and CX3CR1, and pro-inflammatory cytokines were analyzed by immunohistochemistry staining. Results: The level of pro-inflammatory cytokines IL-1β, IL-6, TNF-α, FKN, and CX3CR1 were elevated two weeks after fructose feeding. AZD8797 inhibited CX3CR1-microglia, which improved the regulation of systemic blood pressure and NO generation in the NTS. We also found that IL-1β, IL-6, and TNF-α levels were recovered by AZD8797 addition. Conclusion: We conclude that CX3CR1-microglia represses the nNOS signaling pathway and promotes chronic inflammation in fructose-induced hypertension. Collectively, our results reveal the role of chemokines such as IL-1β, IL-6, and TNF-α in NTS neuroinflammation with the involvement of FKN and CX3CR1.

Original languageEnglish
Article number185
JournalJournal of Neuroinflammation
Volume17
Issue number1
DOIs
Publication statusPublished - 2020 Jun 12

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Immunology
  • Neurology
  • Cellular and Molecular Neuroscience

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