8-Nitro-cGMP attenuates context-dependent fear memory in mice

Yusuke Kishimoto, Shingo Kasamatsu, Shuichi Yanai, Shogo Endo, Takaaki Akaike, Hideshi Ihara

Research output: Contribution to journalArticlepeer-review

Abstract

We previously reported that 8-nitroguanosine 3′,5′-cyclic monophosphate (8-nitro-cGMP) is endogenously produced via nitric oxide/reactive oxygen species signaling pathways and it reacts with protein thiol residues to add cGMP structure to proteins through S-guanylation. S-Guanylation occurs on synaptosomal-associated protein 25 (SNAP-25), which is a part of the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex that regulates exocytosis. However, the biological relevance of 8-nitro-cGMP in the nervous system remains unclear. Here, we investigated the effects of intracerebroventricular (icv) infusion of 8-nitro-cGMP on mouse brain functions. The results of an open-field test and fear-conditioning task revealed that icv infusion of 8-nitro-cGMP decreased the vertical activity and context-dependent fear memory of mice, which are both associated with the hippocampus. Immunohistochemical analysis revealed increased c-Fos-positive cells in the dentate gyrus in 8-nitro-cGMP-infused mice. Further, biochemical analyses showed that icv infusion of 8-nitro-cGMP increased S-guanylated proteins including SNAP-25 and SNARE complex formation as well as decreased complexes containing complexin, which regulates exocytosis by binding to the SNARE complex, in the hippocampus. These findings suggest that accumulation of 8-nitro-cGMP in the hippocampus affects its functions, including memory, via S-guanylation of hippocampal proteins such as SNAP-25.

Original languageEnglish
Pages (from-to)141-147
Number of pages7
JournalBiochemical and biophysical research communications
Volume511
Issue number1
DOIs
Publication statusPublished - 2019 Mar 26

Keywords

  • 8-Nitroguanosine 3′,5′-cyclic monophosphate
  • Fear-conditioning task
  • Nitric oxide
  • Reactive oxygen species
  • S-Guanylation
  • Synaptosomal-associated protein 25

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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