2024
GeroScience

Expression of alpha smooth muscle actin decreases with ageing and increases upon lumen obstruction in mouse brain pericytes

Authors:

Fanni Győri, Ádám Mészáros, Mónika Krecsmarik, Kinga Molnár, Cornel Balta, Anca Hermenean, Attila E. Farkas, István A. Krizbai, Imola Wilhelm

Keywords:

Ageing brain; Alpha smooth muscle actin (α-SMA); Ensheathing pericyte; Mesh pericyte; Microocclusion

Abstract:

Cerebral pericytes are mural cells covering brain microvessels, organized as ensheathing, mesh and thin-strand pericytes. These latter two, together called capillary pericytes, have low levels of alpha smooth muscle actin (α-SMA), regulating basal vascular tone and applying a slow influence on cerebral blood flow. Pericytes are subject to alterations in ageing which may be even more pronounced in age-related pathologies, including microinfarcts, which usually affect a large number of vessels in the ageing brain. We modelled this condition by injecting 10 µm-size microspheres into the circulation of mice resulting in the occlusion of capillaries covered by ensheathing and mesh pericytes. We observed that α-SMA and Acta2, the gene encoding it, as well as TGF-β1/Tgfb1, the major regulator of α-SMA, decreased during ageing in cerebral microvessels. In the vicinity of the microspheres stalled in the capillaries, expression of α-SMA increased significantly in both ensheathing and especially in mesh pericytes, both in young (2 to 3 months of age) and old (24 months of age) mice. On the other hand, γ-actin was detected in endothelial cells, but not in pericytes, and decreased in microvessels of microsphere-containing hemispheres. Altogether, our data show that obstruction of cerebral microvessels increases α-SMA expression in pericytes in both age groups, but this does not compensate for the lower expression of the contractile protein in old animals. Increased α-SMA expression may lead to constriction of the obstructed vessels probably aggravating flow heterogeneity in the aged brain.