Evaluation of delayed LNFPIII treatment initiation protocol on improving long-term behavioral and neuroinflammatory pathology in a mouse model of Gulf War Illness
Chemical overexposures and war-related stress during the 1990–1991 Gulf War (GW) are implicated in the persisting pathological symptoms that many GW veterans continue to endure. These symptoms culminate into a disease known as Gulf War Illness (GWI) and affect about a third of the GW veteran populat...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-12-01
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| Series: | Brain, Behavior, & Immunity - Health |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666354622001430 |
| _version_ | 1797991164196945920 |
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| author | Jessica M. Carpenter Kyle A. Brown Lukas Veltmaat Helaina D. Ludwig Kendall B. Clay Thomas Norberg Donald A. Harn John J. Wagner Nikolay M. Filipov |
| author_facet | Jessica M. Carpenter Kyle A. Brown Lukas Veltmaat Helaina D. Ludwig Kendall B. Clay Thomas Norberg Donald A. Harn John J. Wagner Nikolay M. Filipov |
| author_sort | Jessica M. Carpenter |
| collection | DOAJ |
| description | Chemical overexposures and war-related stress during the 1990–1991 Gulf War (GW) are implicated in the persisting pathological symptoms that many GW veterans continue to endure. These symptoms culminate into a disease known as Gulf War Illness (GWI) and affect about a third of the GW veteran population. Currently, comprehensive effective GWI treatment options are unavailable. Here, an established GWI mouse model was utilized to explore the (1) long-term behavioral and neuroinflammatory effects of deployment-related GWI chemicals exposure and (2) ability of the immunotherapeutic lacto-N-fucopentaose III (LNFPIII) to improve deficits when given months after the end of exposure. Male C57BL6/J mice (8–9 weeks old) were administered pyridostigmine bromide (PB) and DEET for 14 days along with corticosterone (CORT; latter 7 days) to emulate wartime stress. On day 15, a single injection of the nerve agent surrogate diisopropylfluorophosphate (DFP) was given. LNFPIII treatment began 7 months post GWI chemicals exposure and continued until study completion. A battery of behavioral tests for assessment of cognition/memory, mood, and motor function in rodents was performed beginning 8 months after exposure termination and was then followed by immunohistochemcal evaluation of neuroinflammation and neurogenesis. Within tests of motor function, prior GWI chemical exposure led to hyperactivity, impaired sensorimotor function, and altered gait. LNFPIII attenuated these motor-related deficits and improved overall grip strength. GWI mice also exhibited more anxiety-like behavior that was reduced by LNFPIII; this was test-specific. Short-term, but not long-term memory, was impaired by prior GWI exposure; LNFPIII improved this measure. In the brains of GWI mice, but not in mice treated with LNFPIII, glial activation was increased. Overall, it appears that months after exposure to GWI chemicals, behavioral deficits and neuroinflammation are present. Many of these deficits were attenuated by LNFPIII when treatment began long after GWI chemical exposure termination, highlighting its therapeutic potential for veterans with GWI. |
| first_indexed | 2024-04-11T08:48:09Z |
| format | Article |
| id | doaj.art-0312f7a6c1c84860974d2129e6bb005d |
| institution | Directory Open Access Journal |
| issn | 2666-3546 |
| language | English |
| last_indexed | 2024-04-11T08:48:09Z |
| publishDate | 2022-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Brain, Behavior, & Immunity - Health |
| spelling | doaj.art-0312f7a6c1c84860974d2129e6bb005d2022-12-22T04:33:53ZengElsevierBrain, Behavior, & Immunity - Health2666-35462022-12-0126100553Evaluation of delayed LNFPIII treatment initiation protocol on improving long-term behavioral and neuroinflammatory pathology in a mouse model of Gulf War IllnessJessica M. Carpenter0Kyle A. Brown1Lukas Veltmaat2Helaina D. Ludwig3Kendall B. Clay4Thomas Norberg5Donald A. Harn6John J. Wagner7Nikolay M. Filipov8Department of Physiology and Pharmacology, University of Georgia, Athens, GA, United States; Neuroscience Program, University of Georgia, Athens, GA, United StatesDepartment of Physiology and Pharmacology, University of Georgia, Athens, GA, United StatesDepartment of Physiology and Pharmacology, University of Georgia, Athens, GA, United StatesDepartment of Physiology and Pharmacology, University of Georgia, Athens, GA, United StatesNeuroscience Program, University of Georgia, Athens, GA, United StatesDepartment of Chemistry, University of Uppsala, Uppsala, SwedenDepartment of Infectious Diseases and Center for Tropical and Emerging Diseases, University of Georgia, Athens, GA, United StatesDepartment of Physiology and Pharmacology, University of Georgia, Athens, GA, United States; Neuroscience Program, University of Georgia, Athens, GA, United StatesDepartment of Physiology and Pharmacology, University of Georgia, Athens, GA, United States; Neuroscience Program, University of Georgia, Athens, GA, United States; Corresponding author. Department of Physiology and Pharmacology, 501 DW Brooks Drive, Athens, GA, 30602, United States.Chemical overexposures and war-related stress during the 1990–1991 Gulf War (GW) are implicated in the persisting pathological symptoms that many GW veterans continue to endure. These symptoms culminate into a disease known as Gulf War Illness (GWI) and affect about a third of the GW veteran population. Currently, comprehensive effective GWI treatment options are unavailable. Here, an established GWI mouse model was utilized to explore the (1) long-term behavioral and neuroinflammatory effects of deployment-related GWI chemicals exposure and (2) ability of the immunotherapeutic lacto-N-fucopentaose III (LNFPIII) to improve deficits when given months after the end of exposure. Male C57BL6/J mice (8–9 weeks old) were administered pyridostigmine bromide (PB) and DEET for 14 days along with corticosterone (CORT; latter 7 days) to emulate wartime stress. On day 15, a single injection of the nerve agent surrogate diisopropylfluorophosphate (DFP) was given. LNFPIII treatment began 7 months post GWI chemicals exposure and continued until study completion. A battery of behavioral tests for assessment of cognition/memory, mood, and motor function in rodents was performed beginning 8 months after exposure termination and was then followed by immunohistochemcal evaluation of neuroinflammation and neurogenesis. Within tests of motor function, prior GWI chemical exposure led to hyperactivity, impaired sensorimotor function, and altered gait. LNFPIII attenuated these motor-related deficits and improved overall grip strength. GWI mice also exhibited more anxiety-like behavior that was reduced by LNFPIII; this was test-specific. Short-term, but not long-term memory, was impaired by prior GWI exposure; LNFPIII improved this measure. In the brains of GWI mice, but not in mice treated with LNFPIII, glial activation was increased. Overall, it appears that months after exposure to GWI chemicals, behavioral deficits and neuroinflammation are present. Many of these deficits were attenuated by LNFPIII when treatment began long after GWI chemical exposure termination, highlighting its therapeutic potential for veterans with GWI.http://www.sciencedirect.com/science/article/pii/S2666354622001430Gulf war illnessLNFPIIIPesticidesBehaviorNeuroinflammationNeurogenesis |
| spellingShingle | Jessica M. Carpenter Kyle A. Brown Lukas Veltmaat Helaina D. Ludwig Kendall B. Clay Thomas Norberg Donald A. Harn John J. Wagner Nikolay M. Filipov Evaluation of delayed LNFPIII treatment initiation protocol on improving long-term behavioral and neuroinflammatory pathology in a mouse model of Gulf War Illness Brain, Behavior, & Immunity - Health Gulf war illness LNFPIII Pesticides Behavior Neuroinflammation Neurogenesis |
| title | Evaluation of delayed LNFPIII treatment initiation protocol on improving long-term behavioral and neuroinflammatory pathology in a mouse model of Gulf War Illness |
| title_full | Evaluation of delayed LNFPIII treatment initiation protocol on improving long-term behavioral and neuroinflammatory pathology in a mouse model of Gulf War Illness |
| title_fullStr | Evaluation of delayed LNFPIII treatment initiation protocol on improving long-term behavioral and neuroinflammatory pathology in a mouse model of Gulf War Illness |
| title_full_unstemmed | Evaluation of delayed LNFPIII treatment initiation protocol on improving long-term behavioral and neuroinflammatory pathology in a mouse model of Gulf War Illness |
| title_short | Evaluation of delayed LNFPIII treatment initiation protocol on improving long-term behavioral and neuroinflammatory pathology in a mouse model of Gulf War Illness |
| title_sort | evaluation of delayed lnfpiii treatment initiation protocol on improving long term behavioral and neuroinflammatory pathology in a mouse model of gulf war illness |
| topic | Gulf war illness LNFPIII Pesticides Behavior Neuroinflammation Neurogenesis |
| url | http://www.sciencedirect.com/science/article/pii/S2666354622001430 |
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