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Histamine 2/3 receptor agonists alleviate perioperative neurocognitive disorders by inhibiting microglia activation through the PI3K/AKT/FoxO1 pathway in aged rats.
Chen, Yi-Nan; Sha, Huan-Huan; Wang, Yi-Wei; Zhou, Qin; Bhuiyan, Piplu; Li, Na-Na; Qian, Yan-Ning; Dong, Hong-Quan.
Affiliation
  • Chen YN; Department of Anesthesiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu, People's Republic of China.
  • Sha HH; Department of Anesthesiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu, People's Republic of China.
  • Wang YW; Department of Anesthesiology, Wuxi People's Hospital, Wuxi, 214001, Jiangsu, People's Republic of China.
  • Zhou Q; Department of Anesthesiology, Jiangsu Cancer Hospital, Nanjing, 210009, Jiangsu, People's Republic of China.
  • Bhuiyan P; Department of Anesthesiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu, People's Republic of China.
  • Li NN; Department of Anesthesiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu, People's Republic of China.
  • Qian YN; Department of Anesthesiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu, People's Republic of China.
  • Dong HQ; Department of Anesthesiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu, People's Republic of China. dhqmzys@163.com.
J Neuroinflammation ; 17(1): 217, 2020 Jul 22.
Article in En | MEDLINE | ID: mdl-32698899
ABSTRACT

BACKGROUND:

Microglia, the principal sentinel immune cells of the central nervous system (CNS), play an extensively vital role in neuroinflammation and perioperative neurocognitive disorders (PND). Histamine, a potent mediator of inflammation, can both promote and prevent microglia-related neuroinflammation by activating different histamine receptors. Rat microglia express four histamine receptors (H1R, H2R, H3R, and H4R), among which the histamine 1 and 4 receptors can promote microglia activation, whereas the role and cellular mechanism of the histamine 2 and 3 receptors have not been elucidated. Therefore, we evaluated the effects and potential cellular mechanisms of histamine 2/3 receptors in microglia-mediated inflammation and PND.

METHODS:

This study investigated the role of histamine 2/3 receptors in microglia-induced inflammation and PND both in vivo and in vitro. In the in vivo experiments, rats were injected with histamine 2/3 receptor agonists in the right lateral ventricle and were then subjected to exploratory laparotomy. In the in vitro experiments, primary microglia were pretreated with histamine 2/3 receptor agonists before stimulation with lipopolysaccharide (LPS). Cognitive function, microglia activation, proinflammatory cytokine production, NF-κb expression, M1/M2 phenotypes, cell migration, and Toll-like receptor-4 (TLR4) expression were assessed.

RESULTS:

In our study, the histamine 2/3 receptor agonists inhibited exploratory laparotomy- or LPS-induced cognitive decline, microglia activation, proinflammatory cytokine production, NF-κb expression, M1/M2 phenotype transformation, cell migration, and TLR4 expression through the PI3K/AKT/FoxO1 pathway.

CONCLUSION:

Based on our findings, we conclude that histamine 2/3 receptors ameliorate PND by inhibiting microglia activation through the PI3K/AKT/FoxO1 pathway. Our results highlight histamine 2/3 receptors as potential therapeutic targets to treat neurological conditions associated with PND.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Histamine Agonists / Microglia / Postoperative Cognitive Complications Limits: Animals Language: En Journal: J Neuroinflammation Journal subject: NEUROLOGIA Year: 2020 Type: Article

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Histamine Agonists / Microglia / Postoperative Cognitive Complications Limits: Animals Language: En Journal: J Neuroinflammation Journal subject: NEUROLOGIA Year: 2020 Type: Article