Serotonin 5-HT2A receptor expression is chronically decreased in the anterior cerebral cortex of male rats following repetitive low-level blast exposure
IntroductionMany Veterans who experienced blast-related traumatic brain injuries (TBIs) in Iraq and Afghanistan currently suffer from chronic cognitive and mental health problems that include depression and post-traumatic stress disorder (PTSD). Male rats exposed to repetitive low-level blast develo...
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Frontiers Media S.A.
2025-06-01
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| Series: | Frontiers in Neurology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fneur.2025.1594335/full |
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| author | Rita De Gasperi Rita De Gasperi Georgina Perez Garcia Georgina Perez Garcia Miguel A. Gama Sosa Miguel A. Gama Sosa Gissel M. Perez Rania Abutarboush Rania Abutarboush Usmah Kawoos Usmah Kawoos Patrick R. Hof Patrick R. Hof Patrick R. Hof Carolyn W. Zhu Carolyn W. Zhu Carolyn W. Zhu Stephen T. Ahlers Gregory A. Elder Gregory A. Elder Gregory A. Elder Gregory A. Elder |
| author_facet | Rita De Gasperi Rita De Gasperi Georgina Perez Garcia Georgina Perez Garcia Miguel A. Gama Sosa Miguel A. Gama Sosa Gissel M. Perez Rania Abutarboush Rania Abutarboush Usmah Kawoos Usmah Kawoos Patrick R. Hof Patrick R. Hof Patrick R. Hof Carolyn W. Zhu Carolyn W. Zhu Carolyn W. Zhu Stephen T. Ahlers Gregory A. Elder Gregory A. Elder Gregory A. Elder Gregory A. Elder |
| author_sort | Rita De Gasperi |
| collection | DOAJ |
| description | IntroductionMany Veterans who experienced blast-related traumatic brain injuries (TBIs) in Iraq and Afghanistan currently suffer from chronic cognitive and mental health problems that include depression and post-traumatic stress disorder (PTSD). Male rats exposed to repetitive low-level blast develop chronic cognitive and PTSD-related behavioral traits that are present for more than 1 year after exposure. Psychedelic agents alter cognition as well as mood and agents such as psilocybin have gained attention as possible treatments for the mental health disorders that affect Veterans. The best-known action of psilocybin’s metabolite psilocin is to stimulate the serotonin 2A receptor (5-HT2AR). The aim of this study was to determine whether 5-HT2AR levels are altered by blast exposure.Methods5-HT2AR expression was examined by Western blot in 7 cohorts of rats exposed to low level repetitive blast collected from 2 weeks to 12 months after blast exposure. The analysis included three brain regions (anterior cerebral cortex, hippocampus and amygdala) that were chosen based on being relevant to fear learning and the biological basis of PTSD. Possible correlations between Western blot data and behavioral outcomes were evaluated.Results5-HT2AR was chronically decreased in anterior cortex of blast-exposed rats in all cohorts except the one studied at 2 weeks after blast exposure. 5-HT2AR levels were variably affected in the other regions. 5-HT2AR expression correlated differently in blast and control rats in some behavioral parameters.ConclusionThese findings have implications for understanding the neurochemical basis of blast-induced cognitive and behavioral changes. They also suggest 5-HT2AR as a potential therapeutic target for treatment of PTSD-related symptoms that follow blast injury. |
| format | Article |
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| language | English |
| publishDate | 2025-06-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Neurology |
| spelling | doaj-art-1a44a5a971b142a69c8a3c09aa9afba42025-06-25T04:10:23ZengFrontiers Media S.A.Frontiers in Neurology1664-22952025-06-011610.3389/fneur.2025.15943351594335Serotonin 5-HT2A receptor expression is chronically decreased in the anterior cerebral cortex of male rats following repetitive low-level blast exposureRita De Gasperi0Rita De Gasperi1Georgina Perez Garcia2Georgina Perez Garcia3Miguel A. Gama Sosa4Miguel A. Gama Sosa5Gissel M. Perez6Rania Abutarboush7Rania Abutarboush8Usmah Kawoos9Usmah Kawoos10Patrick R. Hof11Patrick R. Hof12Patrick R. Hof13Carolyn W. Zhu14Carolyn W. Zhu15Carolyn W. Zhu16Stephen T. Ahlers17Gregory A. Elder18Gregory A. Elder19Gregory A. Elder20Gregory A. Elder21Research and Development Service, James J. Peters Department of Veterans Affairs Medical Center, Bronx, NY, United StatesDepartment of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, United StatesResearch and Development Service, James J. Peters Department of Veterans Affairs Medical Center, Bronx, NY, United StatesDepartment of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, United StatesDepartment of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, United StatesGeneral Medical Research Service, James J. Peters Department of Veterans Affairs Medical Center, Bronx, NY, United StatesResearch and Development Service, James J. Peters Department of Veterans Affairs Medical Center, Bronx, NY, United StatesDepartment of Neurotrauma, Naval Medical Research Command, Silver Spring, MD, United StatesThe Henry M. Jackson Foundation for the Advancement of Military Medicine Inc., Bethesda, MD, United StatesDepartment of Neurotrauma, Naval Medical Research Command, Silver Spring, MD, United StatesThe Henry M. Jackson Foundation for the Advancement of Military Medicine Inc., Bethesda, MD, United StatesNash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, United StatesDepartment of Geriatrics and Palliative Care, Icahn School of Medicine at Mount Sinai, New York, NY, United StatesMount Sinai Alzheimer’s Disease Research Center and Ronald M. Loeb Center for Alzheimer’s Disease, Icahn School of Medicine at Mount Sinai, New York, NY, United StatesResearch and Development Service, James J. Peters Department of Veterans Affairs Medical Center, Bronx, NY, United StatesDepartment of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, United StatesMount Sinai Alzheimer’s Disease Research Center and Ronald M. Loeb Center for Alzheimer’s Disease, Icahn School of Medicine at Mount Sinai, New York, NY, United StatesDepartment of Neurotrauma, Naval Medical Research Command, Silver Spring, MD, United StatesDepartment of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, United StatesDepartment of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, United StatesMount Sinai Alzheimer’s Disease Research Center and Ronald M. Loeb Center for Alzheimer’s Disease, Icahn School of Medicine at Mount Sinai, New York, NY, United States0Neurology Service, James J. Peters Department of Veterans Affairs Medical Center, Bronx, NY, United StatesIntroductionMany Veterans who experienced blast-related traumatic brain injuries (TBIs) in Iraq and Afghanistan currently suffer from chronic cognitive and mental health problems that include depression and post-traumatic stress disorder (PTSD). Male rats exposed to repetitive low-level blast develop chronic cognitive and PTSD-related behavioral traits that are present for more than 1 year after exposure. Psychedelic agents alter cognition as well as mood and agents such as psilocybin have gained attention as possible treatments for the mental health disorders that affect Veterans. The best-known action of psilocybin’s metabolite psilocin is to stimulate the serotonin 2A receptor (5-HT2AR). The aim of this study was to determine whether 5-HT2AR levels are altered by blast exposure.Methods5-HT2AR expression was examined by Western blot in 7 cohorts of rats exposed to low level repetitive blast collected from 2 weeks to 12 months after blast exposure. The analysis included three brain regions (anterior cerebral cortex, hippocampus and amygdala) that were chosen based on being relevant to fear learning and the biological basis of PTSD. Possible correlations between Western blot data and behavioral outcomes were evaluated.Results5-HT2AR was chronically decreased in anterior cortex of blast-exposed rats in all cohorts except the one studied at 2 weeks after blast exposure. 5-HT2AR levels were variably affected in the other regions. 5-HT2AR expression correlated differently in blast and control rats in some behavioral parameters.ConclusionThese findings have implications for understanding the neurochemical basis of blast-induced cognitive and behavioral changes. They also suggest 5-HT2AR as a potential therapeutic target for treatment of PTSD-related symptoms that follow blast injury.https://www.frontiersin.org/articles/10.3389/fneur.2025.1594335/fullblastserotonin 5-HT2A receptormale ratsmilitary Veteranstraumatic brain injury |
| spellingShingle | Rita De Gasperi Rita De Gasperi Georgina Perez Garcia Georgina Perez Garcia Miguel A. Gama Sosa Miguel A. Gama Sosa Gissel M. Perez Rania Abutarboush Rania Abutarboush Usmah Kawoos Usmah Kawoos Patrick R. Hof Patrick R. Hof Patrick R. Hof Carolyn W. Zhu Carolyn W. Zhu Carolyn W. Zhu Stephen T. Ahlers Gregory A. Elder Gregory A. Elder Gregory A. Elder Gregory A. Elder Serotonin 5-HT2A receptor expression is chronically decreased in the anterior cerebral cortex of male rats following repetitive low-level blast exposure Frontiers in Neurology blast serotonin 5-HT2A receptor male rats military Veterans traumatic brain injury |
| title | Serotonin 5-HT2A receptor expression is chronically decreased in the anterior cerebral cortex of male rats following repetitive low-level blast exposure |
| title_full | Serotonin 5-HT2A receptor expression is chronically decreased in the anterior cerebral cortex of male rats following repetitive low-level blast exposure |
| title_fullStr | Serotonin 5-HT2A receptor expression is chronically decreased in the anterior cerebral cortex of male rats following repetitive low-level blast exposure |
| title_full_unstemmed | Serotonin 5-HT2A receptor expression is chronically decreased in the anterior cerebral cortex of male rats following repetitive low-level blast exposure |
| title_short | Serotonin 5-HT2A receptor expression is chronically decreased in the anterior cerebral cortex of male rats following repetitive low-level blast exposure |
| title_sort | serotonin 5 ht2a receptor expression is chronically decreased in the anterior cerebral cortex of male rats following repetitive low level blast exposure |
| topic | blast serotonin 5-HT2A receptor male rats military Veterans traumatic brain injury |
| url | https://www.frontiersin.org/articles/10.3389/fneur.2025.1594335/full |
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