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

Yusuke Kishimoto1, Shingo Kasamatsu2, Shuichi Yanai3

  • 1Department of Biological Science, Graduate School of Science, Osaka Prefecture University, Sakai, Osaka 599-8531, Japan.

Biochemical and Biophysical Research Communications
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PubMed
Summary

8-nitro-cGMP accumulation in the brain impairs memory and activity by modifying proteins like SNAP-25 in the hippocampus. This S-guanylation process affects crucial brain functions.

Keywords:
8-Nitroguanosine 3′,5′-cyclic monophosphateFear-conditioning taskNitric oxideReactive oxygen speciesS-GuanylationSynaptosomal-associated protein 25

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Area of Science:

  • Neuroscience
  • Biochemistry
  • Molecular Biology

Background:

  • 8-nitroguanosine 3',5'-cyclic monophosphate (8-nitro-cGMP) is produced via nitric oxide/reactive oxygen species pathways.
  • S-guanylation modifies proteins, including SNAP-25 in the SNARE complex, impacting exocytosis.

Purpose of the Study:

  • To investigate the biological relevance of 8-nitro-cGMP in the nervous system.
  • To determine the effects of intracerebroventricular 8-nitro-cGMP infusion on mouse brain functions.

Main Methods:

  • Intracerebroventricular (icv) infusion of 8-nitro-cGMP in mice.
  • Open-field test and fear-conditioning tasks.
  • Immunohistochemistry and biochemical analyses (Western blotting).

Main Results:

  • icv 8-nitro-cGMP infusion decreased vertical activity and context-dependent fear memory.
  • Increased c-Fos-positive cells observed in the dentate gyrus.
  • Elevated S-guanylated proteins (SNAP-25) and SNARE complex formation, with decreased complexin association in the hippocampus.

Conclusions:

  • Hippocampal accumulation of 8-nitro-cGMP impairs brain functions, including memory.
  • S-guanylation of hippocampal proteins like SNAP-25 mediates these effects.
  • 8-nitro-cGMP influences exocytosis regulation within the hippocampus.