HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Ibrutinib alleviates LPS-induced neuroinflammation and synaptic defects in a mouse model of depression.

Abstract
Previous studies have demonstrated a close association between an altered immune system and major depressive disorders, and inhibition of neuroinflammation may represent an alternative mechanism to treat depression. Recently, the anti-inflammatory activity of ibrutinib has been reported. However, the effect of ibrutinib on neuroinflammation-induced depression and its underlying mechanism has not been comprehensively studied. Therefore, we aimed to elucidate the potential anti-depressive role and mechanism of ibrutinib against neuroinflammation-induced depression and synaptic defects. Our results showed that ibrutinib treatment significantly reduced lipopolysaccharide (LPS)-induced depressive-like behaviors and neuroinflammation via inhibiting NF-kB activation, decreasing proinflammatory cytokine levels, and normalizing redox signaling and its downstream components, including Nrf2, HO-1, and SOD2, as well as glial cell activation markers, such as Iba-1 and GFAP. Further, ibrutinib treatment inhibited LPS-activated inflammasome activation by targeting NLRP3/P38/Caspase-1 signaling. Interestingly, LPS reduced the number of dendritic spines and expression of BDNF, and synaptic-related markers, including PSD95, snap25, and synaptophysin, were improved by ibrutinib treatment in the hippocampal area of the mouse brain. In conclusion, our findings suggest that ibrutinib can alleviate neuroinflammation and synaptic defects, suggesting it has antidepressant potential against LPS-induced neuroinflammation and depression.
AuthorsWeifen Li, Tahir Ali, Kaiwu He, Zizhen Liu, Fawad Ali Shah, Qingguo Ren, Yan Liu, Anlong Jiang, Shupeng Li
JournalBrain, behavior, and immunity (Brain Behav Immun) Vol. 92 Pg. 10-24 (02 2021) ISSN: 1090-2139 [Electronic] Netherlands
PMID33181270 (Publication Type: Journal Article)
CopyrightCopyright © 2020 Elsevier Inc. All rights reserved.
Chemical References
  • Inflammasomes
  • Lipopolysaccharides
  • Piperidines
  • ibrutinib
  • Adenine
Topics
  • Adenine (analogs & derivatives)
  • Animals
  • Depression (chemically induced, drug therapy)
  • Depressive Disorder, Major
  • Inflammasomes
  • Lipopolysaccharides
  • Mice
  • Piperidines

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: