Restoring tripartite glutamatergic synapses: A potential therapy for mood and cognitive deficits in Gulf War illness
Gulf War illness is associated with a combination of exposure to war-related chemical agents and traumatic stress. Currently, there are no effective treatments, and the pathophysiology remains elusive. Neurological problems are among the most commonly reported symptoms. In this study, we investigate...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2020-11-01
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| Series: | Neurobiology of Stress |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352289520300308 |
| _version_ | 1818613351341621248 |
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| author | Xueqin Wang Zan Xu Fangli Zhao Kuanhung J. Lin Joshua B. Foster Tianqi Xiao Nydia Kung Candice C. Askwith John P. Bruno Valentina Valentini Kevin J. Hodgetts Chien-liang Glenn Lin |
| author_facet | Xueqin Wang Zan Xu Fangli Zhao Kuanhung J. Lin Joshua B. Foster Tianqi Xiao Nydia Kung Candice C. Askwith John P. Bruno Valentina Valentini Kevin J. Hodgetts Chien-liang Glenn Lin |
| author_sort | Xueqin Wang |
| collection | DOAJ |
| description | Gulf War illness is associated with a combination of exposure to war-related chemical agents and traumatic stress. Currently, there are no effective treatments, and the pathophysiology remains elusive. Neurological problems are among the most commonly reported symptoms. In this study, we investigated the glutamatergic system in the hippocampi of mice exposed to war-related chemical agents and stress. Mice developed Gulf War illness-like symptoms, including mood deficits, cognitive impairments, and fatigue. They exhibited the following pathological changes in hippocampi: elevated extracellular glutamate levels, impaired glutamatergic synapses, astrocyte atrophy, loss of interneurons, and decreased neurogenesis. LDN/OSU-215111 is a small-molecule that can strengthen the structure and function of both the astrocytic processes and the glutamatergic synapses that together form the tripartite synapses. We found that LDN/OSU-215111 effectively prevented the development of mood and cognitive deficits in mice when treatment was implemented immediately following the exposure. Moreover, when symptoms were already present, LDN/OSU-215111 still significantly ameliorated these deficits; impressively, benefits were sustained one month after treatment cessation, indicating disease modification. LDN/OSU-215111 effectively normalized hippocampal pathological changes. Overall, this study provides strong evidence that restoration of tripartite glutamatergic synapses by LDN/OSU-215111 is a potential therapy for Gulf War illness. |
| first_indexed | 2024-12-16T16:00:44Z |
| format | Article |
| id | doaj.art-812793df0d1541d792d7a3180e11545f |
| institution | Directory Open Access Journal |
| issn | 2352-2895 |
| language | English |
| last_indexed | 2024-12-16T16:00:44Z |
| publishDate | 2020-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Stress |
| spelling | doaj.art-812793df0d1541d792d7a3180e11545f2022-12-21T22:25:28ZengElsevierNeurobiology of Stress2352-28952020-11-0113100240Restoring tripartite glutamatergic synapses: A potential therapy for mood and cognitive deficits in Gulf War illnessXueqin Wang0Zan Xu1Fangli Zhao2Kuanhung J. Lin3Joshua B. Foster4Tianqi Xiao5Nydia Kung6Candice C. Askwith7John P. Bruno8Valentina Valentini9Kevin J. Hodgetts10Chien-liang Glenn Lin11Department of Neuroscience, College of Medicine, The Ohio State University, Columbus, OH, USADepartment of Neuroscience, College of Medicine, The Ohio State University, Columbus, OH, USADepartment of Neuroscience, College of Medicine, The Ohio State University, Columbus, OH, USADepartment of Neuroscience, College of Medicine, The Ohio State University, Columbus, OH, USADepartment of Neuroscience, College of Medicine, The Ohio State University, Columbus, OH, USADepartment of Neuroscience, College of Medicine, The Ohio State University, Columbus, OH, USADepartment of Neuroscience, College of Medicine, The Ohio State University, Columbus, OH, USADepartment of Neuroscience, College of Medicine, The Ohio State University, Columbus, OH, USADepartment of Neuroscience, College of Medicine, The Ohio State University, Columbus, OH, USA; Department of Psychology, College of Arts and Sciences, The Ohio State University, Columbus, OH, USADepartment of Psychology, College of Arts and Sciences, The Ohio State University, Columbus, OH, USA; Department of Biomedical Sciences, University of Cagliari, ItalyDepartment of Neurology, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA, USADepartment of Neuroscience, College of Medicine, The Ohio State University, Columbus, OH, USA; Corresponding author. Graves Hall 4066D, 333 W. 10th Ave, Columbus, OH, 43210, USA.Gulf War illness is associated with a combination of exposure to war-related chemical agents and traumatic stress. Currently, there are no effective treatments, and the pathophysiology remains elusive. Neurological problems are among the most commonly reported symptoms. In this study, we investigated the glutamatergic system in the hippocampi of mice exposed to war-related chemical agents and stress. Mice developed Gulf War illness-like symptoms, including mood deficits, cognitive impairments, and fatigue. They exhibited the following pathological changes in hippocampi: elevated extracellular glutamate levels, impaired glutamatergic synapses, astrocyte atrophy, loss of interneurons, and decreased neurogenesis. LDN/OSU-215111 is a small-molecule that can strengthen the structure and function of both the astrocytic processes and the glutamatergic synapses that together form the tripartite synapses. We found that LDN/OSU-215111 effectively prevented the development of mood and cognitive deficits in mice when treatment was implemented immediately following the exposure. Moreover, when symptoms were already present, LDN/OSU-215111 still significantly ameliorated these deficits; impressively, benefits were sustained one month after treatment cessation, indicating disease modification. LDN/OSU-215111 effectively normalized hippocampal pathological changes. Overall, this study provides strong evidence that restoration of tripartite glutamatergic synapses by LDN/OSU-215111 is a potential therapy for Gulf War illness.http://www.sciencedirect.com/science/article/pii/S2352289520300308Gulf war illnessTraumatic stressMood deficits and cognitive impairmentsTripartite glutamatergic synapsesTherapy |
| spellingShingle | Xueqin Wang Zan Xu Fangli Zhao Kuanhung J. Lin Joshua B. Foster Tianqi Xiao Nydia Kung Candice C. Askwith John P. Bruno Valentina Valentini Kevin J. Hodgetts Chien-liang Glenn Lin Restoring tripartite glutamatergic synapses: A potential therapy for mood and cognitive deficits in Gulf War illness Neurobiology of Stress Gulf war illness Traumatic stress Mood deficits and cognitive impairments Tripartite glutamatergic synapses Therapy |
| title | Restoring tripartite glutamatergic synapses: A potential therapy for mood and cognitive deficits in Gulf War illness |
| title_full | Restoring tripartite glutamatergic synapses: A potential therapy for mood and cognitive deficits in Gulf War illness |
| title_fullStr | Restoring tripartite glutamatergic synapses: A potential therapy for mood and cognitive deficits in Gulf War illness |
| title_full_unstemmed | Restoring tripartite glutamatergic synapses: A potential therapy for mood and cognitive deficits in Gulf War illness |
| title_short | Restoring tripartite glutamatergic synapses: A potential therapy for mood and cognitive deficits in Gulf War illness |
| title_sort | restoring tripartite glutamatergic synapses a potential therapy for mood and cognitive deficits in gulf war illness |
| topic | Gulf war illness Traumatic stress Mood deficits and cognitive impairments Tripartite glutamatergic synapses Therapy |
| url | http://www.sciencedirect.com/science/article/pii/S2352289520300308 |
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