Cargando…
Modulation of astrocyte activity and improvement of oxidative stress through blockage of NO/NMDAR pathway improve posttraumatic stress disorder (PTSD)‐like behavior induced by social isolation stress
BACKGROUND: It has been well documented that social isolation stress (SIS) can induce posttraumatic stress disorder (PTSD)‐like behavior in rodents, however, the underlying mechanism is remained misunderstood. In the current study, we aimed to elucidate the role of NO/NMDAR pathway in PTSD‐like beha...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9304825/ https://www.ncbi.nlm.nih.gov/pubmed/35605060 http://dx.doi.org/10.1002/brb3.2620 |
_version_ | 1784752177595547648 |
---|---|
author | Li, Hua Tofigh, Arash Mohammadi Amirfakhraei, Azita Chen, Xuan Tajik, Michael Xu, Dongwei Motevalli, Saeid |
author_facet | Li, Hua Tofigh, Arash Mohammadi Amirfakhraei, Azita Chen, Xuan Tajik, Michael Xu, Dongwei Motevalli, Saeid |
author_sort | Li, Hua |
collection | PubMed |
description | BACKGROUND: It has been well documented that social isolation stress (SIS) can induce posttraumatic stress disorder (PTSD)‐like behavior in rodents, however, the underlying mechanism is remained misunderstood. In the current study, we aimed to elucidate the role of NO/NMDAR pathway in PTSD‐like behavior through modulating of astrocyte activity and improvement of oxidative stress. METHODS: Male NMRI mice were used to evaluate the memory function by using Morris water maze (MWM) and fear memory extinction by using freezing response. We used MK‐801 (NMDAR‐antagonist), L‐NNA (NOS‐inhibitor), NMDA (NMDAR‐agonist), and L‐arginine (NO‐agent) to find a proper treatment. Also, immunohistochemistry, RT‐PCR, and oxidative stress assays were used to evaluate the levels of astrocytes and oxidative stress. We used five mice in each experimental task. RESULTS: Our results revealed that SIS could induce learning and memory dysfunction as well as impairment of fear memory extinction in MWM and freezing response tests, respectively. Also, we observed that combined treatment including blockage of NOS (by L‐NNA, 0.5 mg/kg) and NMDAR (by MK‐801, 0.001 mg/kg) at subeffective doses could result in improvement of both memory and fear memory. In addition, we observed that SIS significantly increases the GFAP expression and astrocyte activity, which results in significant imbalance in oxidative stress. Coadministration of MK‐801 and L‐NNA at subeffective doses not only decreases the expression of GFAP, but also regulates the oxidative stress imbalance CONCLUSION: Based on these results, it could be hypothesized that blockage of NO/NMDAR pathway might be a novel treatment for PTSD‐like behavior in animals by inhibiting the astrocyte and regulating oxidative stress level. |
format | Online Article Text |
id | pubmed-9304825 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-93048252022-07-26 Modulation of astrocyte activity and improvement of oxidative stress through blockage of NO/NMDAR pathway improve posttraumatic stress disorder (PTSD)‐like behavior induced by social isolation stress Li, Hua Tofigh, Arash Mohammadi Amirfakhraei, Azita Chen, Xuan Tajik, Michael Xu, Dongwei Motevalli, Saeid Brain Behav Original Articles BACKGROUND: It has been well documented that social isolation stress (SIS) can induce posttraumatic stress disorder (PTSD)‐like behavior in rodents, however, the underlying mechanism is remained misunderstood. In the current study, we aimed to elucidate the role of NO/NMDAR pathway in PTSD‐like behavior through modulating of astrocyte activity and improvement of oxidative stress. METHODS: Male NMRI mice were used to evaluate the memory function by using Morris water maze (MWM) and fear memory extinction by using freezing response. We used MK‐801 (NMDAR‐antagonist), L‐NNA (NOS‐inhibitor), NMDA (NMDAR‐agonist), and L‐arginine (NO‐agent) to find a proper treatment. Also, immunohistochemistry, RT‐PCR, and oxidative stress assays were used to evaluate the levels of astrocytes and oxidative stress. We used five mice in each experimental task. RESULTS: Our results revealed that SIS could induce learning and memory dysfunction as well as impairment of fear memory extinction in MWM and freezing response tests, respectively. Also, we observed that combined treatment including blockage of NOS (by L‐NNA, 0.5 mg/kg) and NMDAR (by MK‐801, 0.001 mg/kg) at subeffective doses could result in improvement of both memory and fear memory. In addition, we observed that SIS significantly increases the GFAP expression and astrocyte activity, which results in significant imbalance in oxidative stress. Coadministration of MK‐801 and L‐NNA at subeffective doses not only decreases the expression of GFAP, but also regulates the oxidative stress imbalance CONCLUSION: Based on these results, it could be hypothesized that blockage of NO/NMDAR pathway might be a novel treatment for PTSD‐like behavior in animals by inhibiting the astrocyte and regulating oxidative stress level. John Wiley and Sons Inc. 2022-05-23 /pmc/articles/PMC9304825/ /pubmed/35605060 http://dx.doi.org/10.1002/brb3.2620 Text en © 2022 The Authors. Brain and Behavior published by Wiley Periodicals LLC. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Articles Li, Hua Tofigh, Arash Mohammadi Amirfakhraei, Azita Chen, Xuan Tajik, Michael Xu, Dongwei Motevalli, Saeid Modulation of astrocyte activity and improvement of oxidative stress through blockage of NO/NMDAR pathway improve posttraumatic stress disorder (PTSD)‐like behavior induced by social isolation stress |
title | Modulation of astrocyte activity and improvement of oxidative stress through blockage of NO/NMDAR pathway improve posttraumatic stress disorder (PTSD)‐like behavior induced by social isolation stress |
title_full | Modulation of astrocyte activity and improvement of oxidative stress through blockage of NO/NMDAR pathway improve posttraumatic stress disorder (PTSD)‐like behavior induced by social isolation stress |
title_fullStr | Modulation of astrocyte activity and improvement of oxidative stress through blockage of NO/NMDAR pathway improve posttraumatic stress disorder (PTSD)‐like behavior induced by social isolation stress |
title_full_unstemmed | Modulation of astrocyte activity and improvement of oxidative stress through blockage of NO/NMDAR pathway improve posttraumatic stress disorder (PTSD)‐like behavior induced by social isolation stress |
title_short | Modulation of astrocyte activity and improvement of oxidative stress through blockage of NO/NMDAR pathway improve posttraumatic stress disorder (PTSD)‐like behavior induced by social isolation stress |
title_sort | modulation of astrocyte activity and improvement of oxidative stress through blockage of no/nmdar pathway improve posttraumatic stress disorder (ptsd)‐like behavior induced by social isolation stress |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9304825/ https://www.ncbi.nlm.nih.gov/pubmed/35605060 http://dx.doi.org/10.1002/brb3.2620 |
work_keys_str_mv | AT lihua modulationofastrocyteactivityandimprovementofoxidativestressthroughblockageofnonmdarpathwayimproveposttraumaticstressdisorderptsdlikebehaviorinducedbysocialisolationstress AT tofigharashmohammadi modulationofastrocyteactivityandimprovementofoxidativestressthroughblockageofnonmdarpathwayimproveposttraumaticstressdisorderptsdlikebehaviorinducedbysocialisolationstress AT amirfakhraeiazita modulationofastrocyteactivityandimprovementofoxidativestressthroughblockageofnonmdarpathwayimproveposttraumaticstressdisorderptsdlikebehaviorinducedbysocialisolationstress AT chenxuan modulationofastrocyteactivityandimprovementofoxidativestressthroughblockageofnonmdarpathwayimproveposttraumaticstressdisorderptsdlikebehaviorinducedbysocialisolationstress AT tajikmichael modulationofastrocyteactivityandimprovementofoxidativestressthroughblockageofnonmdarpathwayimproveposttraumaticstressdisorderptsdlikebehaviorinducedbysocialisolationstress AT xudongwei modulationofastrocyteactivityandimprovementofoxidativestressthroughblockageofnonmdarpathwayimproveposttraumaticstressdisorderptsdlikebehaviorinducedbysocialisolationstress AT motevallisaeid modulationofastrocyteactivityandimprovementofoxidativestressthroughblockageofnonmdarpathwayimproveposttraumaticstressdisorderptsdlikebehaviorinducedbysocialisolationstress |