Increased Caveolin-2 Expression in Brain Endothelial Cells Promotes Age-Related Neuroinflammation

Abstract

Aging is a major risk factor for common neurodegenerative diseases. Although multiple molecular, cellular, structural, and functional changes occur in the brain during aging, the involvement of caveolin-2 (Cav-2) in brain ageing remains unknown. We investigated Cav-2 expression in brains of aged mice and its effects on endothelial cells. The human umbilical vein endothelial cells (HUVECs) showed decreased THP-1 adhesion and infiltration when treated with Cav-2 siRNA compared to control siRNA. In contrast, Cav-2 overexpression increased THP-1 adhesion and infiltration in HUVECs. Increased expression of Cav-2 and iba-1 was observed in brains of old mice. Moreover, there were fewer iba-1-positive cells in the brains of aged Cav-2 knockout (KO) mice than of wild-type aged mice. The levels of several chemokines were higher in brains of aged wild-type mice than in young wildtype mice; moreover, chemokine levels were significantly lower in brains of young mice as well as aged Cav-2 KO mice than in their wild-type counterparts. Expression of PECAM1 and VE-cadherin proteins increased in brains of old wildtype mice but was barely detected in brains of young wildtype and Cav-2 KO mice. Collectively, our results suggest that Cav-2 expression increases in the endothelial cells of aged brain, and promotes leukocyte infiltration and age-associated neuroinflammation.

Age- and Sex-Dependent Caveolar Gene Expression in Normoxic and Post-Ischemic Mouse Hearts

“…We also noticed a decline in expression of Cav2 with aging in the normoxic male heart (but not females), previously Cav-2 overexpression has been shown to major be a regulator of longevity and stress adaptation in C. elegans (Mehta et al, 2016). In an aging model of the mouse brain, Cav2 transcript & protein was found to be up-regulated which was associated with age-related neuroinflammation (Park et al, 2022). In contrast, a recent study suggested a protective role of Cav2 in an intestinal model of I-R injury where infiltrating cytotoxically activated leukocytes were found in Cav2 -deficient mice subjected to I-R which were associated with enhanced leukocyte rolling, adhesion and injury (Liu et al, 2021).…”

“…We also noticed a decline in expression of Cav2 with aging in the normoxic male heart (but not females), previously Cav-2 overexpression has been shown to major be a regulator of longevity and stress adaptation in C. elegans et al, 2016). In an aging model of the mouse brain, Cav2 transcript & protein was found to be up-regulated which was associated with age-related neuroinflammation (Park et al, 2022). In contrast, a recent study suggested a protective role of…”