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Title: Disrupting nNOS-PSD-95 coupling in the hippocampal dentate gyrus promotes extinction memory retrieval

Abstract

Granule cells in the dentate gyrus regenerate constantly in adult hippocampus and then integrate into neural circuits in the hippocampus thereby providing the neural basis for learning and memory. Promoting the neurogenesis in the hippocampus facilitates learning and memory such as spatial learning, object identification, and extinction learning. The interaction between neuronal nitric oxide synthase (nNOS) and postsynaptic density protein-95 (PSD-95) is reported to negatively regulate neurogenesis in brain, so we hypothesized that disrupting this interaction might facilitate the neurogenesis in the dentate gyrus (DG) and thus enhance the extinction memory retrieval of fear learning. We found that uncoupling the nNOS-PSD-95 complex in remote contextual fear condition promoted both neuronal proliferation and survival in the DG, contributing to an enhanced retrieval of the extinction memory. Moreover, the nNOS-PSD-95 uncoupling-induced neurogenesis may be mediated by the extracellular signal-regulated kinase (ERK) as the phosphorylation level of ERK1/2 was increased after uncoupling. These findings suggest that the nNOS-PSD-95 complex may serve as a novel target for the treatment of post-traumatic stress disorder (PTSD). - Highlights: • nNOS-PSD-95 disruption promoted neurogenesis in the DG. • Delayed disruption of nNOS-PSD-95 still enhanced remote contextual fear extinction. • The enhancement of fear extinction relied on neuronalmore » proliferation. • nNOS-PSD-95 disruption increased ERK1/2 phosphorylation.« less

Authors:
; ; ; ;  [1];  [2];  [3]; ; ;  [1];  [2];  [1];  [2];  [2]
  1. Department of Pharmacology, School of Pharmacy, Nanjing Medical University, Nanjing 211166 (China)
  2. (China)
  3. Department of Medicinal Chemistry, School of Pharmacy, Nanjing Medical University, Nanjing 211166 (China)
Publication Date:
OSTI Identifier:
22719135
Resource Type:
Journal Article
Journal Name:
Biochemical and Biophysical Research Communications
Additional Journal Information:
Journal Volume: 493; Journal Issue: 1; Other Information: Copyright (c) 2017 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0006-291X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; COUPLING; HIPPOCAMPUS; LEARNING; NITRIC OXIDE; PHOSPHORYLATION; PHOSPHOTRANSFERASES

Citation Formats

Li, Jun, Han, Zhou, Cao, Bo, Cai, Cheng-Yun, Lin, Yu-Hui, Institution of Stem Cells and Neuroregeneration, Nanjing Medical University, Nanjing 211166, Li, Fei, Wu, Hai-Ying, Chang, Lei, Luo, Chun-Xia, Institution of Stem Cells and Neuroregeneration, Nanjing Medical University, Nanjing 211166, Zhu, Dong-Ya, Institution of Stem Cells and Neuroregeneration, Nanjing Medical University, Nanjing 211166, and The Key Laboratory of Precision Medicine of Cardiovascular Disease, Nanjing 211166. Disrupting nNOS-PSD-95 coupling in the hippocampal dentate gyrus promotes extinction memory retrieval. United States: N. p., 2017. Web. doi:10.1016/J.BBRC.2017.09.003.
Li, Jun, Han, Zhou, Cao, Bo, Cai, Cheng-Yun, Lin, Yu-Hui, Institution of Stem Cells and Neuroregeneration, Nanjing Medical University, Nanjing 211166, Li, Fei, Wu, Hai-Ying, Chang, Lei, Luo, Chun-Xia, Institution of Stem Cells and Neuroregeneration, Nanjing Medical University, Nanjing 211166, Zhu, Dong-Ya, Institution of Stem Cells and Neuroregeneration, Nanjing Medical University, Nanjing 211166, & The Key Laboratory of Precision Medicine of Cardiovascular Disease, Nanjing 211166. Disrupting nNOS-PSD-95 coupling in the hippocampal dentate gyrus promotes extinction memory retrieval. United States. doi:10.1016/J.BBRC.2017.09.003.
Li, Jun, Han, Zhou, Cao, Bo, Cai, Cheng-Yun, Lin, Yu-Hui, Institution of Stem Cells and Neuroregeneration, Nanjing Medical University, Nanjing 211166, Li, Fei, Wu, Hai-Ying, Chang, Lei, Luo, Chun-Xia, Institution of Stem Cells and Neuroregeneration, Nanjing Medical University, Nanjing 211166, Zhu, Dong-Ya, Institution of Stem Cells and Neuroregeneration, Nanjing Medical University, Nanjing 211166, and The Key Laboratory of Precision Medicine of Cardiovascular Disease, Nanjing 211166. Sat . "Disrupting nNOS-PSD-95 coupling in the hippocampal dentate gyrus promotes extinction memory retrieval". United States. doi:10.1016/J.BBRC.2017.09.003.
@article{osti_22719135,
title = {Disrupting nNOS-PSD-95 coupling in the hippocampal dentate gyrus promotes extinction memory retrieval},
author = {Li, Jun and Han, Zhou and Cao, Bo and Cai, Cheng-Yun and Lin, Yu-Hui and Institution of Stem Cells and Neuroregeneration, Nanjing Medical University, Nanjing 211166 and Li, Fei and Wu, Hai-Ying and Chang, Lei and Luo, Chun-Xia and Institution of Stem Cells and Neuroregeneration, Nanjing Medical University, Nanjing 211166 and Zhu, Dong-Ya and Institution of Stem Cells and Neuroregeneration, Nanjing Medical University, Nanjing 211166 and The Key Laboratory of Precision Medicine of Cardiovascular Disease, Nanjing 211166},
abstractNote = {Granule cells in the dentate gyrus regenerate constantly in adult hippocampus and then integrate into neural circuits in the hippocampus thereby providing the neural basis for learning and memory. Promoting the neurogenesis in the hippocampus facilitates learning and memory such as spatial learning, object identification, and extinction learning. The interaction between neuronal nitric oxide synthase (nNOS) and postsynaptic density protein-95 (PSD-95) is reported to negatively regulate neurogenesis in brain, so we hypothesized that disrupting this interaction might facilitate the neurogenesis in the dentate gyrus (DG) and thus enhance the extinction memory retrieval of fear learning. We found that uncoupling the nNOS-PSD-95 complex in remote contextual fear condition promoted both neuronal proliferation and survival in the DG, contributing to an enhanced retrieval of the extinction memory. Moreover, the nNOS-PSD-95 uncoupling-induced neurogenesis may be mediated by the extracellular signal-regulated kinase (ERK) as the phosphorylation level of ERK1/2 was increased after uncoupling. These findings suggest that the nNOS-PSD-95 complex may serve as a novel target for the treatment of post-traumatic stress disorder (PTSD). - Highlights: • nNOS-PSD-95 disruption promoted neurogenesis in the DG. • Delayed disruption of nNOS-PSD-95 still enhanced remote contextual fear extinction. • The enhancement of fear extinction relied on neuronal proliferation. • nNOS-PSD-95 disruption increased ERK1/2 phosphorylation.},
doi = {10.1016/J.BBRC.2017.09.003},
journal = {Biochemical and Biophysical Research Communications},
issn = {0006-291X},
number = 1,
volume = 493,
place = {United States},
year = {2017},
month = {11}
}