Mast cell deficiency improves cognition and enhances disease-associated microglia in 5XFAD mice
Summary: Emerging evidence suggests that peripheral immune cells contribute to Alzheimer’s disease (AD) neuropathogenesis. Among these, mast cells are known for their functions in allergic reactions and neuroinflammation; however, little is known about their role in AD. Here, we crossed 5XFAD mice w...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-09-01
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| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124723011531 |
| _version_ | 1797685268080230400 |
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| author | Chih-Chung Jerry Lin Fanny Herisson Hoang Le Nader Jaafar Kashish Chetal Mary K. Oram Kelly L. Flynn Evan P. Gavrilles Ruslan I. Sadreyev Felipe L. Schiffino Rudolph E. Tanzi |
| author_facet | Chih-Chung Jerry Lin Fanny Herisson Hoang Le Nader Jaafar Kashish Chetal Mary K. Oram Kelly L. Flynn Evan P. Gavrilles Ruslan I. Sadreyev Felipe L. Schiffino Rudolph E. Tanzi |
| author_sort | Chih-Chung Jerry Lin |
| collection | DOAJ |
| description | Summary: Emerging evidence suggests that peripheral immune cells contribute to Alzheimer’s disease (AD) neuropathogenesis. Among these, mast cells are known for their functions in allergic reactions and neuroinflammation; however, little is known about their role in AD. Here, we crossed 5XFAD mice with mast cell-deficient strains and observed the effects on AD-related neuropathology and cognitive impairment. We found that mast cell depletion improved contextual fear conditioning in 5XFAD mice without affecting cued fear conditioning, anxiety-like behavior, or amyloid burden. Furthermore, mast cell depletion led to an upregulation of transcriptomic signatures for putatively protective disease-associated microglia and resulted in reduced markers indicative of reactive astrocytes. We hypothesize a system of bidirectional communication between dural mast cells and the brain, where mast cells respond to signals from the brain environment by expressing immune-regulatory mediators, impacting cognition and glial cell function. These findings highlight mast cells as potential therapeutic targets for AD. |
| first_indexed | 2024-03-12T00:42:42Z |
| format | Article |
| id | doaj.art-ebc21dd290af4b188e93315e9f2e49f6 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-03-12T00:42:42Z |
| publishDate | 2023-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-ebc21dd290af4b188e93315e9f2e49f62023-09-15T04:39:30ZengElsevierCell Reports2211-12472023-09-01429113141Mast cell deficiency improves cognition and enhances disease-associated microglia in 5XFAD miceChih-Chung Jerry Lin0Fanny Herisson1Hoang Le2Nader Jaafar3Kashish Chetal4Mary K. Oram5Kelly L. Flynn6Evan P. Gavrilles7Ruslan I. Sadreyev8Felipe L. Schiffino9Rudolph E. Tanzi10Genetics and Aging Research Unit, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USAGenetics and Aging Research Unit, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USAGenetics and Aging Research Unit, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USAGenetics and Aging Research Unit, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USADepartment of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USAGenetics and Aging Research Unit, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USAGenetics and Aging Research Unit, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USAGenetics and Aging Research Unit, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USADepartment of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USAGenetics and Aging Research Unit, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USAGenetics and Aging Research Unit, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA; Henry and Allison McCance Center for Brain Health, Massachusetts General Hospital, Charlestown, MA 02129, USA; Corresponding authorSummary: Emerging evidence suggests that peripheral immune cells contribute to Alzheimer’s disease (AD) neuropathogenesis. Among these, mast cells are known for their functions in allergic reactions and neuroinflammation; however, little is known about their role in AD. Here, we crossed 5XFAD mice with mast cell-deficient strains and observed the effects on AD-related neuropathology and cognitive impairment. We found that mast cell depletion improved contextual fear conditioning in 5XFAD mice without affecting cued fear conditioning, anxiety-like behavior, or amyloid burden. Furthermore, mast cell depletion led to an upregulation of transcriptomic signatures for putatively protective disease-associated microglia and resulted in reduced markers indicative of reactive astrocytes. We hypothesize a system of bidirectional communication between dural mast cells and the brain, where mast cells respond to signals from the brain environment by expressing immune-regulatory mediators, impacting cognition and glial cell function. These findings highlight mast cells as potential therapeutic targets for AD.http://www.sciencedirect.com/science/article/pii/S2211124723011531CP: NeuroscienceCP: Immunology |
| spellingShingle | Chih-Chung Jerry Lin Fanny Herisson Hoang Le Nader Jaafar Kashish Chetal Mary K. Oram Kelly L. Flynn Evan P. Gavrilles Ruslan I. Sadreyev Felipe L. Schiffino Rudolph E. Tanzi Mast cell deficiency improves cognition and enhances disease-associated microglia in 5XFAD mice Cell Reports CP: Neuroscience CP: Immunology |
| title | Mast cell deficiency improves cognition and enhances disease-associated microglia in 5XFAD mice |
| title_full | Mast cell deficiency improves cognition and enhances disease-associated microglia in 5XFAD mice |
| title_fullStr | Mast cell deficiency improves cognition and enhances disease-associated microglia in 5XFAD mice |
| title_full_unstemmed | Mast cell deficiency improves cognition and enhances disease-associated microglia in 5XFAD mice |
| title_short | Mast cell deficiency improves cognition and enhances disease-associated microglia in 5XFAD mice |
| title_sort | mast cell deficiency improves cognition and enhances disease associated microglia in 5xfad mice |
| topic | CP: Neuroscience CP: Immunology |
| url | http://www.sciencedirect.com/science/article/pii/S2211124723011531 |
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