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Article

Immunohistochemical Study of ASC Expression and Distribution in the Hippocampus of an Aged Murine Model of Alzheimer’s Disease

by
Diana Reimers
1,*,
Manuela Vallejo-Muñoz
1,
María José Casarejos
1,
Adriano Jimenez-Escrig
1,2,
Rafael Gonzalo-Gobernado
1,3 and
Eulalia Bazan
1
1
Servicio de Neurobiología, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), 28034 Madrid, Spain
2
Servicio de Neurología, Hospital Ramón y Cajal, 28034 Madrid, Spain
3
National Center for Biotechnology (CNB), Consejo Superior de Investigaciones Científicas CSIC, 28049 Madrid, Spain
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2021, 22(16), 8697; https://doi.org/10.3390/ijms22168697
Submission received: 15 July 2021 / Accepted: 10 August 2021 / Published: 13 August 2021
(This article belongs to the Special Issue Microglia Heterogeneity and Its Relevance for Translational Research)

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.
Keywords: Alzheimer’s disease; neuroinflammation; innate immunity; ASC; inflammasomes; amyloid β plaques; microglia; astroglia; hippocampal interneurons; age Alzheimer’s disease; neuroinflammation; innate immunity; ASC; inflammasomes; amyloid β plaques; microglia; astroglia; hippocampal interneurons; age

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MDPI and ACS Style

Reimers, D.; Vallejo-Muñoz, M.; Casarejos, M.J.; Jimenez-Escrig, A.; Gonzalo-Gobernado, R.; Bazan, E. Immunohistochemical Study of ASC Expression and Distribution in the Hippocampus of an Aged Murine Model of Alzheimer’s Disease. Int. J. Mol. Sci. 2021, 22, 8697. https://doi.org/10.3390/ijms22168697

AMA Style

Reimers D, Vallejo-Muñoz M, Casarejos MJ, Jimenez-Escrig A, Gonzalo-Gobernado R, Bazan E. Immunohistochemical Study of ASC Expression and Distribution in the Hippocampus of an Aged Murine Model of Alzheimer’s Disease. International Journal of Molecular Sciences. 2021; 22(16):8697. https://doi.org/10.3390/ijms22168697

Chicago/Turabian Style

Reimers, Diana, Manuela Vallejo-Muñoz, María José Casarejos, Adriano Jimenez-Escrig, Rafael Gonzalo-Gobernado, and Eulalia Bazan. 2021. "Immunohistochemical Study of ASC Expression and Distribution in the Hippocampus of an Aged Murine Model of Alzheimer’s Disease" International Journal of Molecular Sciences 22, no. 16: 8697. https://doi.org/10.3390/ijms22168697

APA Style

Reimers, D., Vallejo-Muñoz, M., Casarejos, M. J., Jimenez-Escrig, A., Gonzalo-Gobernado, R., & Bazan, E. (2021). Immunohistochemical Study of ASC Expression and Distribution in the Hippocampus of an Aged Murine Model of Alzheimer’s Disease. International Journal of Molecular Sciences, 22(16), 8697. https://doi.org/10.3390/ijms22168697

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