Neuroinflammation underlies the development of social stress induced cognitive deficit in male sickle cell mice
Cognitive deficit is a debilitating complication of sickle cell disease (SCD), with a multifactorial etiopathogenesis. Here we show that neuroinflammation and dysregulation in lipidomics and transcriptomics profiles are major underlying mechanisms of social stress-induced cognitive deficit in SCD. M...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2024-11-01
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| Series: | Experimental Biology and Medicine |
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| Online Access: | https://www.ebm-journal.org/articles/10.3389/ebm.2024.10361/full |
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| author | S’Dravious A. DeVeaux S’Dravious A. DeVeaux Sofiya Vyshnya Sofiya Vyshnya Katherine Propsom Oluwabukola T. Gbotosho Asem S. Singh Robert Z. Horning Mihika Sharma Anil G. Jegga Liang Niu Edward A. Botchwey Edward A. Botchwey Hyacinth I. Hyacinth |
| author_facet | S’Dravious A. DeVeaux S’Dravious A. DeVeaux Sofiya Vyshnya Sofiya Vyshnya Katherine Propsom Oluwabukola T. Gbotosho Asem S. Singh Robert Z. Horning Mihika Sharma Anil G. Jegga Liang Niu Edward A. Botchwey Edward A. Botchwey Hyacinth I. Hyacinth |
| author_sort | S’Dravious A. DeVeaux |
| collection | DOAJ |
| description | Cognitive deficit is a debilitating complication of sickle cell disease (SCD), with a multifactorial etiopathogenesis. Here we show that neuroinflammation and dysregulation in lipidomics and transcriptomics profiles are major underlying mechanisms of social stress-induced cognitive deficit in SCD. Male Townes sickle cell (SS) mice and controls (AA) were exposed to social stress using the repeat social defeat (RSD) paradigm concurrently with or without treatment with minocycline. Mice were tested for cognitive deficit using novel object recognition and fear conditioning tests. SS mice exposed to RSD without treatment had worse performance on cognitive tests compared to SS mice exposed to RSD with treatment or to AA controls, irrespective of their RSD or treatment disposition. Additionally, compared to SS mice exposed to RSD with treatment, SS mice exposed to RSD without treatment had significantly more cellular evidence of neuroinflammation coupled with a significant shift in the differentiation of neural progenitor cells towards astrogliogenesis. Additionally, brain tissue from SS mice exposed to RSD was significantly enriched for genes associated with blood-brain barrier dysfunction, neuron excitotoxicity, inflammation, and significant dysregulation in sphingolipids important to neuronal cell processes. We demonstrate in this study that social stress induces cognitive deficit in SS mice, concurrently with neuroinflammation and lipid dysregulation. |
| format | Article |
| id | doaj-art-cf60ae327363473aad9f9b4733f4237f |
| institution | Kabale University |
| issn | 1535-3699 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Experimental Biology and Medicine |
| spelling | doaj-art-cf60ae327363473aad9f9b4733f4237f2024-11-19T11:55:05ZengFrontiers Media S.A.Experimental Biology and Medicine1535-36992024-11-0124910.3389/ebm.2024.1036110361Neuroinflammation underlies the development of social stress induced cognitive deficit in male sickle cell miceS’Dravious A. DeVeaux0S’Dravious A. DeVeaux1Sofiya Vyshnya2Sofiya Vyshnya3Katherine Propsom4Oluwabukola T. Gbotosho5Asem S. Singh6Robert Z. Horning7Mihika Sharma8Anil G. Jegga9Liang Niu10Edward A. Botchwey11Edward A. Botchwey12Hyacinth I. Hyacinth13The Wallace H. Coulter Department of Biomedical Engineering, Georgia Tech and Emory, Atlanta, GA, United StatesPetit Institute of Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta, GA, United StatesThe Wallace H. Coulter Department of Biomedical Engineering, Georgia Tech and Emory, Atlanta, GA, United StatesPetit Institute of Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta, GA, United StatesDepartment of Neurology and Rehabilitation Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, United StatesDepartment of Neurology and Rehabilitation Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, United StatesDepartment of Neurology and Rehabilitation Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, United StatesDepartment of Neurology and Rehabilitation Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, United StatesDivision of Biomedical Informatics, Department of Pediatrics, Cincinnati Children’s Hospital Medical Center, University of Cincinnati College of Medicine Cincinnati, Cincinnati, OH, United StatesDivision of Biomedical Informatics, Department of Pediatrics, Cincinnati Children’s Hospital Medical Center, University of Cincinnati College of Medicine Cincinnati, Cincinnati, OH, United StatesDepartment of Environmental and Public Health Sciences, University of Cincinnati College of Medicine, Cincinnati, OH, United StatesThe Wallace H. Coulter Department of Biomedical Engineering, Georgia Tech and Emory, Atlanta, GA, United StatesPetit Institute of Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta, GA, United StatesDepartment of Neurology and Rehabilitation Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, United StatesCognitive deficit is a debilitating complication of sickle cell disease (SCD), with a multifactorial etiopathogenesis. Here we show that neuroinflammation and dysregulation in lipidomics and transcriptomics profiles are major underlying mechanisms of social stress-induced cognitive deficit in SCD. Male Townes sickle cell (SS) mice and controls (AA) were exposed to social stress using the repeat social defeat (RSD) paradigm concurrently with or without treatment with minocycline. Mice were tested for cognitive deficit using novel object recognition and fear conditioning tests. SS mice exposed to RSD without treatment had worse performance on cognitive tests compared to SS mice exposed to RSD with treatment or to AA controls, irrespective of their RSD or treatment disposition. Additionally, compared to SS mice exposed to RSD with treatment, SS mice exposed to RSD without treatment had significantly more cellular evidence of neuroinflammation coupled with a significant shift in the differentiation of neural progenitor cells towards astrogliogenesis. Additionally, brain tissue from SS mice exposed to RSD was significantly enriched for genes associated with blood-brain barrier dysfunction, neuron excitotoxicity, inflammation, and significant dysregulation in sphingolipids important to neuronal cell processes. We demonstrate in this study that social stress induces cognitive deficit in SS mice, concurrently with neuroinflammation and lipid dysregulation.https://www.ebm-journal.org/articles/10.3389/ebm.2024.10361/fullsickle cell diseaseneuroinflammationcognitive functionsocial stressminocycline |
| spellingShingle | S’Dravious A. DeVeaux S’Dravious A. DeVeaux Sofiya Vyshnya Sofiya Vyshnya Katherine Propsom Oluwabukola T. Gbotosho Asem S. Singh Robert Z. Horning Mihika Sharma Anil G. Jegga Liang Niu Edward A. Botchwey Edward A. Botchwey Hyacinth I. Hyacinth Neuroinflammation underlies the development of social stress induced cognitive deficit in male sickle cell mice Experimental Biology and Medicine sickle cell disease neuroinflammation cognitive function social stress minocycline |
| title | Neuroinflammation underlies the development of social stress induced cognitive deficit in male sickle cell mice |
| title_full | Neuroinflammation underlies the development of social stress induced cognitive deficit in male sickle cell mice |
| title_fullStr | Neuroinflammation underlies the development of social stress induced cognitive deficit in male sickle cell mice |
| title_full_unstemmed | Neuroinflammation underlies the development of social stress induced cognitive deficit in male sickle cell mice |
| title_short | Neuroinflammation underlies the development of social stress induced cognitive deficit in male sickle cell mice |
| title_sort | neuroinflammation underlies the development of social stress induced cognitive deficit in male sickle cell mice |
| topic | sickle cell disease neuroinflammation cognitive function social stress minocycline |
| url | https://www.ebm-journal.org/articles/10.3389/ebm.2024.10361/full |
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