Primary mouse brain pericytes isolated from transgenic Alzheimer mice spontaneously differentiate into a CD11b+ microglial-like cell type in vitro

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Abstract

Alzheimer's disease (AD) is characterized by amyloid-β plaques, tau pathology and vascular impairment including pericyte damage. Pericytes are perivascular cells of the blood-brain barrier and can differentiate into different cell types in vitro including microglia. The aim of the present study is to explore if primary mouse brain pericytes isolated and cultured from transgenic AD (APP_SweDI) mice can differentiate into CD11b+ (integrin alpha M) microglia in vitro. We show that primary pericytes (passage 5) isolated from wildtype C57BL6 mice differentiated into CD11b+ microglia (Type B, >90%), when exposed to a differentiation factor mix of FGF-2, cAMP and fibronectin. This differentiation was time-dependent and seen as a large 80kDa CD11b fragment (days 1–8) and a smaller 50kDA CD11b fragment (>4days). These pericytes did not differentiate into neurons, astroglia or oligodendroglia. However, pericytes isolated from transgenic AD mice differentiated into CD11b+ microglia (Type A, <10%) without addition of exogenous differentiation factors, displayed moderate Iba1+ immunostaining and phagocytic activity, but were still positive for PDGFRβ. In conclusion, we show for the first time that primary mouse pericytes from AD mice have the potential to spontanously differentiate in vitro into a CD11b+ microglial-like (Type A) cell type, but we do not provide evidence that these pericytic microglia display a full active microglial cell.

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