Work

An Investigation of the Inflammatory Landscape in the Brain and Bone Marrow of the APP/PS1 Mouse

Year: 2024

Type: article

Abstract: Background: The APP/PS1 mouse model recapitulates pathology of human Alzheimer’s disease (AD). While amyloid-β peptide deposition and neurodegeneration are features of AD, the pathology may involve inflammation and impaired vascular regeneration. Objective: This study evaluated inflammatory environments in the brain and bone marrow (BM), and the impact on brain microvascular density. Methods: BM and frontal cortex from male nine-month-old APP/PS1 or the control C57Bl6/j mice were studied. Vascular density and inflammatory cells were evaluated in the sections of frontal cortex by immunohistochemistry. Different subsets of hematopoietic stem/progenitor cells (BM) and monocyte-macrophages were characterized by flow cytometry and by clonogenic assays. Myelopoietic or inflammatory factors were evaluated by real-time RT-PCR or by western blotting. Results: CD34 + or CD31 + vascular structures were lower ( p < 0.01, n = 6) in the frontal cortex that was associated with decreased number of Lin − Sca-1 + cKit + vasculogenic progenitor cells in the BM and circulation ( p < 0.02, n = 6) compared to the control. Multipotent progenitor cells MPP4, common lymphoid, common myeloid and myeloid progenitor cells were higher in the APP/PS1-BM compared to the control, which agreed with increased numbers of monocytes and pro-inflammatory macrophages. The expression of pro-myelopoietic factors and alarmins was higher in the APP/PS1 BM-HSPCs or in the BM-supernatants compared to the control. Frontal cortices of APP/PS1 mice showed higher number of pro-inflammatory macrophages (CD11b + F4/80 + or CD80 + ) and microglia (OX42 + Iba1 + ). Conclusions: These findings show that AD pathology in APP/PS1 mice is associated with upregulated myelopoiesis, which contributes to the brain inflammation and decreased vascularity.

Source: Journal of Alzheimer s Disease Reports

DOI: 10.3233/adr-240024

Authors: Kishore Chittimalli, Stephen Adkins, Sanjay Arora, Jagdish Singh, Yagna P.R. Jarajapu

Institutions: North Dakota State University, University of North Dakota

Language: English

Topic: Neuroinflammation and Neurodegeneration Mechanisms

Subfield: Neurology

Field: Neuroscience

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: diamond

Funders: National Institutes of Health, National Institute on Aging, National Institute of General Medical Sciences