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Microglia demonstrate local mixed inflammation and a defined morphological shift in an APP/PS1 mouse model

Citation

Holloway, OG and King, AE and Ziebell, JM, Microglia demonstrate local mixed inflammation and a defined morphological shift in an APP/PS1 mouse model, Journal of Alzheimer's Disease, 77, (4) pp. 1765-1781. ISSN 1387-2877 (2020) [Refereed Article]


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Copyright Statement

© 2020 IOS Press and the authors. The final publication is available at IOS Press through http://dx.doi.org/10.3233/JAD-200098

DOI: doi:10.3233/JAD-200098

Abstract

Background: Microglia are traditionally described as the immune cells of the brain and have an inflammatory role in Alzheimer's disease (AD). Microglial morphological and phenotypic shifts in AD have not been fully characterized; however, microglia are often described as either pro- or anti-inflammatory.

Objective: To determine microglial if microglial morphology and phenotype changes with disease status.

Methods: This study observed morphology through Iba1 immunohistochemistry on tissue sections encompassing the primary motor cortex and somatosensory barrel fields. Immunohistochemistry for pro-inflammatory markers: CD14 and CD40; and anti-inflammatory markers: CD16 and TREM2, was performed at 3, 6, and 12 months of age which correlated with pre-plaque, onset, and significant plaque load in APP/PS1 brains (n = 6) and compared to age-matched littermate controls (n = 6).

Results: Microglia demonstrated a defined morphological shift with time. Deramified morphologies increased in the APP/PS1, at both 6 months (p < 0.0001) and 12 months (p < 0.0001). At 12 months, there were significantly lower numbers of ramified microglia (p < 0.001). Results indicated that microglia have a heterogenic marker immunoreactivity as CD16, TREM2, and CD40 were associated with an activated morphology at the same time points. All inflammatory markers were significantly upregulated at 12 months in the APP/PS1 mice (TREM2 (F (2,30) = 10.75, p = 0.0003), CD40 (F (2,30) = 15.86, p < 0.0001), CD14 (F (2,30) = 6.84, p = 0.0036), and CD16 (F (2,30) = 3.026, p = 0.0635)).

Conclusion: Our data indicate that pro- and anti-inflammatory factors of microglia occur in APP/PS1 mice.

Item Details

Item Type:Refereed Article
Keywords:Alzheimer’s disease, anti-inflammatory, microglia, morphology, phenotype, pro-inflammatory
Research Division:Biomedical and Clinical Sciences
Research Group:Neurosciences
Research Field:Central nervous system
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Holloway, OG (Miss Olivia Holloway)
UTAS Author:King, AE (Professor Anna King)
UTAS Author:Ziebell, JM (Dr Jenna Ziebell)
ID Code:140943
Year Published:2020
Deposited By:Wicking Dementia Research and Education Centre
Deposited On:2020-09-15
Last Modified:2021-02-25
Downloads:0

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