1. Immunohistochemical Study of ASC Expression and Distribution in the Hippocampus of an Aged Murine Model of Alzheimer’s Disease
- Author
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Manuela Vallejo-Muñoz, Eulalia Bazán, María José Casarejos, Diana Reimers, Rafael Gonzalo-Gobernado, and Adriano Jimenez-Escrig
- Subjects
Genetically modified mouse ,Male ,QH301-705.5 ,microglia ,Inflammation ,Mice, Transgenic ,Cytoplasmic Granules ,ASC ,Hippocampus ,Catalysis ,Article ,neuroinflammation ,Inorganic Chemistry ,Pathogenesis ,Amyloid beta-Protein Precursor ,Mice ,Alzheimer Disease ,medicine ,Animals ,Humans ,Biology (General) ,Physical and Theoretical Chemistry ,inflammasomes ,amyloid β plaques ,QD1-999 ,Molecular Biology ,innate immunity ,Spectroscopy ,Caspase ,Neuroinflammation ,Innate immune system ,biology ,Microglia ,astroglia ,hippocampal interneurons ,Organic Chemistry ,Pattern recognition receptor ,General Medicine ,Computer Science Applications ,Cell biology ,CARD Signaling Adaptor Proteins ,Chemistry ,Disease Models, Animal ,medicine.anatomical_structure ,age ,biology.protein ,medicine.symptom ,Alzheimer’s disease - Abstract
Neuroinflammation is involved in the pathogenesis of neurodegenerative diseases such as Alzheimer’s disease (AD), and is notably dependent on age. One important inflammatory pathway exerted by innate immune cells of the nervous system in response to danger signals is mediated by inflammasomes (IF) and leads to the generation of potent pro-inflammatory cytokines. The protein “apoptosis-associated speck-like protein containing a caspase recruitment domain” (ASC) modulates IF activation but has also other functions which are crucial in AD. We intended to characterize immunohistochemically ASC and pattern recognition receptors (PRR) of IF in the hippocampus (HP) of the transgenic mouse model Tg2576 (APP), in which amyloid-beta (Aβ) pathology is directly dependent on age. We show in old-aged APP a significant amount of ASC in microglia and astrocytes associated withAβ plaques, in the absence of PRR described by others in glial cells. In addition, APP developed foci with clusters of extracellular ASC granules not spatiallyrelated to Aβ plaques, which density correlated with the advanced age of mice and AD development. Clusters were associated withspecific astrocytes characterized by their enlarged ring-shaped process terminals, ASC content, and frequent perivascular location. Their possible implication in ASC clearance and propagation of inflammation is discussed.
- Published
- 2021
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