TY - JOUR
T1 - 8-Nitro-cGMP attenuates context-dependent fear memory in mice
AU - Kishimoto, Yusuke
AU - Kasamatsu, Shingo
AU - Yanai, Shuichi
AU - Endo, Shogo
AU - Akaike, Takaaki
AU - Ihara, Hideshi
N1 - Funding Information:
The authors thank Ms. Tomoko Arasaki (Tokyo Metropolitan Institute of Gerontology) and Dr. Masami Takahashi (Kitasato University) for technical helps and the kind gift of the antibodies. This work was supported in part by a Grant-in-Aid for Scientific Research (B), Challenging Exploratory Research, and Innovative Areas "Oxygen Biology: a new criterion for integrated understanding of life" from the Ministry of Education, Sciences, Sports, Technology (MEXT), Japan to H.I. ( 16H04674 , 16K13089 , 26111011 ); the Smoking Research Foundation to H.I.; Graduate Course for System-inspired Leaders in Material Science (SiMS) of Osaka Prefecture University by MEXT, Japan to Y.K.
Funding Information:
The authors thank Ms. Tomoko Arasaki (Tokyo Metropolitan Institute of Gerontology) and Dr. Masami Takahashi (Kitasato University) for technical helps and the kind gift of the antibodies. This work was supported in part by a Grant-in-Aid for Scientific Research (B), Challenging Exploratory Research, and Innovative Areas “Oxygen Biology: a new criterion for integrated understanding of life” from the Ministry of Education, Sciences, Sports, Technology (MEXT), Japan to H.I. (16H04674, 16K13089, 26111011); the Smoking Research Foundation to H.I.; Graduate Course for System-inspired Leaders in Material Science (SiMS) of Osaka Prefecture University by MEXT, Japan to Y.K.
Publisher Copyright:
© 2019 Elsevier Inc.
PY - 2019/3/26
Y1 - 2019/3/26
N2 - 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.
AB - 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.
KW - 8-Nitroguanosine 3′,5′-cyclic monophosphate
KW - Fear-conditioning task
KW - Nitric oxide
KW - Reactive oxygen species
KW - S-Guanylation
KW - Synaptosomal-associated protein 25
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U2 - 10.1016/j.bbrc.2019.01.138
DO - 10.1016/j.bbrc.2019.01.138
M3 - Article
C2 - 30773263
AN - SCOPUS:85061425947
VL - 511
SP - 141
EP - 147
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 1
ER -