Vascular and metabolic responses to elevated circulating PDGF-BB in mice: A multiparametric MRI study.

Abstract

Elevated circulating platelet-derived growth factor-BB (PDGF-BB) has been implicated in various aged-related pathologies and, therefore, is recognized as a potential pro-aging factor. Despite extensive studies on the pathological characterizations centering PDGF-BB/PDGFRβ signaling alterations, there is limited research on the neurofunctional responses to elevated circulating PDGF-BB, primarily because in-vivo measurements are generally required for studying neurofunction. To address this knowledge gap, we characterized the vascular and metabolic responses to elevated circulating PDGF-BB in vivo using multiparametric non-invasive non-contrast MRI techniques in a conditional Pdgfb transgenic mouse model (Pdgfb^cTG) at 6 months of age. We found that Pdgfb^cTG mice exhibited decreased cerebral blood flow (P = 0.025), elevated oxygen extraction (P = 0.002), and increased metabolic rate of oxygen (P = 0.035), which replicated the changes observed in human aging. Compared to naturally aged mice, the rate of change in vascular and metabolic measurements was prominently higher (≥ 200.3%). Our study provides neurofunctional evidence that elevated circulating PDGF-BB accelerates neurovascular aging.