The α7 nicotinic acetylcholine receptor positive allosteric modulator attenuates lipopolysaccharide-induced activation of hippocampal IκB and CD11b gene expression in mice

Muzaffar Abbas, Sami Alzarea, Roger L. Papke, Shafiqur Rahman

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

We have reported that 3a,4,5,9b-tetrahydro-4-(1-naphthalenyl)-3H-cyclopentan[c]quinoline-8-sulfonamide (TQS), α7 nicotinic acetylcholine receptor (nAChR) positive allosteric modulator (PAM) reduces lipopolysaccharide (LPS)-induced hyperalgesia and allodynia in mice. The objective of the present study was to determine the effects of TQS on LPS-induced activation of hippocampal inhibitor of κB (IκB) and cluster of differentiation 11b (CD11b) gene expression involving hyperalgesia and allodynia in mice. We also examined the effects of TQS on microglial phenotype following LPS administration. Pretreatment of TQS (4 mg/kg) reduced the expressions of IκB and CD11b mRNA. Pretreatment of methyllycaconitine (3 mg/kg), an α7 nAChR antagonist, reversed TQS-induced decrease in IκB and CD11b mRNA expressions in the hippocampus indicating the involvement of α7 nAChR. In addition, TQS (4 mg/kg) reversed the LPS-induced microglial morphological changes. These results suggest that TQS reduces LPS-induced IκB and CD11b gene expression and microglial activation associated with hyperalgesia and allodynia by targeting microglial α7 nAChR in the hippocampus.

Original languageEnglish
Pages (from-to)206-211
Number of pages6
JournalDrug Discoveries and Therapeutics
Volume11
Issue number4
DOIs
StatePublished - 1 Jan 2017
Externally publishedYes

Keywords

  • Nicotinic receptor
  • hippocampus
  • mice
  • microglia
  • pain
  • α7 positive allosteric modulator

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