دورية أكاديمية
Differential effects of chronic immunosuppression on behavioral, epigenetic, and Alzheimer’s disease-associated markers in 3xTg-AD mice
| العنوان: | Differential effects of chronic immunosuppression on behavioral, epigenetic, and Alzheimer’s disease-associated markers in 3xTg-AD mice |
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| المؤلفون: | Minesh Kapadia, M. Firoz Mian, Donglai Ma, Craig P. Hutton, Amber Azam, Klotilda Narkaj, Chuanhai Cao, Breanna Brown, Bernadeta Michalski, David Morgan, Paul Forsythe, Iva B. Zovkic, Margaret Fahnestock, Boris Sakic |
| المصدر: | Alzheimer’s Research & Therapy, Vol 13, Iss 1, Pp 1-22 (2021) |
| بيانات النشر: | BMC, 2021. |
| سنة النشر: | 2021 |
| المجموعة: | LCC:Neurosciences. Biological psychiatry. Neuropsychiatry LCC:Neurology. Diseases of the nervous system |
| مصطلحات موضوعية: | Alzheimer’s disease, 3xTg-AD mice, Autoimmunity, Cyclophosphamide, T lymphocytes, Autoantibodies, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571, Neurology. Diseases of the nervous system, RC346-429 |
| الوصف: | Abstract Background Circulating autoantibodies and sex-dependent discrepancy in prevalence are unexplained phenomena of Alzheimer’s disease (AD). Using the 3xTg-AD mouse model, we reported that adult males show early manifestations of systemic autoimmunity, increased emotional reactivity, enhanced expression of the histone variant macroH2A1 in the cerebral cortex, and loss of plaque/tangle pathology. Conversely, adult females display less severe autoimmunity and retain their AD-like phenotype. This study examines the link between immunity and other traits of the current 3xTg-AD model. Methods Young 3xTg-AD and wild-type mice drank a sucrose-laced 0.4 mg/ml solution of the immunosuppressant cyclophosphamide on weekends for 5 months. After behavioral phenotyping at 2 and 6 months of age, we assessed organ mass, serologic markers of autoimmunity, molecular markers of early AD pathology, and expression of genes associated with neurodegeneration. Results Chronic immunosuppression prevented hematocrit drop and reduced soluble Aβ in 3xTg-AD males while normalizing the expression of histone variant macroH2A1 in 3xTg-AD females. This treatment also reduced hepatosplenomegaly, lowered autoantibody levels, and increased the effector T cell population while decreasing the proportion of regulatory T cells in both sexes. Exposure to cyclophosphamide, however, neither prevented reduced brain mass and BDNF expression nor normalized increased tau and anxiety-related behaviors. Conclusion The results suggest that systemic autoimmunity increases soluble Aβ production and affects transcriptional regulation of macroH2A1 in a sex-related manner. Despite the complexity of multisystem interactions, 3xTg-AD mice can be a useful in vivo model for exploring the regulatory role of autoimmunity in the etiology of AD-like neurodegenerative disorders. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1758-9193 |
| العلاقة: | https://doaj.org/toc/1758-9193Test |
| DOI: | 10.1186/s13195-020-00745-9 |
| الوصول الحر: | https://doaj.org/article/7d635303ac54408691a9fbff0c069179Test |
| رقم الانضمام: | edsdoj.7d635303ac54408691a9fbff0c069179 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 17589193 |
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| DOI: | 10.1186/s13195-020-00745-9 |