Hyperfibrinogenemia-mediated astrocyte activation

Brain Research
Vincent D ClarkDavid Lominadze

Abstract

Fibrinogen (Fg)-containing plaques are associated with memory loss during various inflammatory neurodegenerative diseases such as Alzheimer's disease, multiple sclerosis, stroke, and traumatic brain injury. However, mechanisms of its action in neurovascular unit are not clear. As Fg is a high molecular weight blood protein and cannot translocate far from the vessel after extravasation, we hypothesized that it may interact with astrocytes first causing their activation. Cultured mouse cortical astrocytes were treated with Fg in the presence or absence of function-blocking anti-mouse intercellular adhesion molecule 1 (ICAM-1) antibody, or with medium alone (control). Expressions of ICAM-1 and tyrosine receptor kinase B (TrkB) as markers of astrocyte activation, and phosphorylation of TrkB (pTrkB) were assessed. Fg dose-dependently increased activation of astrocytes defined by their shape change, retraction of processes, and enhanced expressions of ICAM-1 and TrkB, and increased pTrkB. Blocking of ICAM-1 function ameliorated these Fg effects. Data suggest that Fg interacts with astrocytes causing overexpression of ICAM-1 and TrkB, and TrkB phosphorylation, and thus, astrocyte activation. Since TrkB is known to be involved in neuro...Continue Reading

Citations

Jul 23, 2020·Journal of Neurophysiology·Mariam CharkvianiDavid Lominadze
Aug 11, 2020·Molecular Neurobiology·Nurul Sulimai, David Lominadze
Sep 26, 2019·Neural Regeneration Research·Rachel KeryGregory W Kirschen
Jan 5, 2021·Cellular and Molecular Neurobiology·Hui CaoWenting Song
Mar 7, 2021·International Journal of Molecular Sciences·Nurul SulimaiDavid Lominadze
Apr 24, 2021·Toxicological Sciences : an Official Journal of the Society of Toxicology·Ekaterina MostovenkoAndrew K Ottens

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