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http://hdl.handle.net/10609/147662
Title: | Microglial Hyperreactivity Evolved to Immunosuppression in the Hippocampus of a Mouse Model of Accelerated Aging and Alzheimer’s Disease Traits |
Author: | Molina-Martínez, Patricia Corpas, Rubén García-Lara, Elisa Cosín-Tomàs, Marta Cristòfol, Rosa Kaliman, Perla Solà, Carme Molinuevo, José Luis Sanchez-Valle, Raquel Antonell, Anna Llado Plarrumani, Albert Sanfeliu, Coral |
Others: | Consejo Superior de Investigaciones Científicas (CSIC) Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) Universitat Oberta de Catalunya. Estudis de Ciències de la Salut Hospital Clínic de Barcelona Universitat de Barcelona (UB) Centro de Investigación Biomédica en Red de Fragilidad y Envejecimiento Saludable (CIBERFES) |
Citation: | Molina-Martínez, P., Corpas, R., García-Lara, E., Cosín-Tomás, M., Cristòfol, R., Kaliman, P., Solà, C., Molinuevo, J.L., Sánchez-Valle, R., Antonell, A., Lladó, A. & Sanfeliu, C. (2021). Microglial Hyperreactivity Evolved to Immunosuppression in the Hippocampus of a Mouse Model of Accelerated Aging and Alzheimer's Disease Traits. Frontiers in Aging Neuroscience, 12, 1-14. doi: 10.3389/fnagi.2020.622360 |
Abstract: | Neuroinflammation is a risk factor for Alzheimer’s disease (AD). We sought to study the glial derangement in AD using diverse experimental models and human brain tissue. Besides classical pro-inflammatory cytokines, we analyzed chitinase 3 like 1 (CHI3L1 or YKL40) and triggering receptor expressed on myeloid cells 2 (TREM2) that are increasingly being associated with astrogliosis and microgliosis in AD, respectively. The SAMP8 mouse model of accelerated aging and AD traits showed elevated pro-inflammatory cytokines and activated microglia phenotype. Furthermore, 6-month-old SAMP8 showed an exacerbated inflammatory response to peripheral lipopolysaccharide in the hippocampus and null responsiveness at the advanced age (for this strain) of 12 months. Gene expression of TREM2 was increased in the hippocampus of transgenic 5XFAD mice and in the cingulate cortex of autosomal dominant AD patients, and to a lesser extent in aged SAMP8 mice and sporadic early-onset AD patients. However, gene expression of CHI3L1 was increased in mice but not in human AD brain samples. The results support the relevance of microglia activation in the pathways leading to neurodegeneration and suggest diverse neuroinflammatory responses according to the AD process. Therefore, the SAMP8 mouse model with marked alterations in the dynamics of microglia activation and senescence may provide a complementary approach to transgenic mouse models for the study of the neuroinflammatory mechanisms underlying AD risk and progression. |
Keywords: | neuroinflammation SAMP8 mice autosomal dominant Alzheimer’s disease (ADAD) sporadic early-onset Alzheimer’s disease (sEOAD) triggering receptor expressed on myeloid cells 2 (TREM2) |
DOI: | https://doi.org/10.3389/fnagi.2020.622360 |
Document type: | info:eu-repo/semantics/article |
Version: | info:eu-repo/semantics/publishedVersion |
Issue Date: | 28-Jan-2021 |
Publication license: | https://creativecommons.org/licenses/by/4.0/ |
Appears in Collections: | Articles Articles cientÍfics |
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Microglial_Hyperreactivity_Evolved_to_Immunosuppression_in_the_Hippocampus_of_a_Mouse_Model_of_Accelerated_Aging_and_Alzheimer_s_Disease_Traits.pdf | 1,7 MB | Adobe PDF | View/Open |
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