Glycation-mediated matrix remodeling of the brain meningeal membrane

Abstract

A normal functional adaptation that takes place as people age is matrix remodeling. Extracellular matrix (ECM) remodeling linked to aging in the brain has, however, received little attention. The function of brain fibroblasts in ECM remodeling in the brain has been addressed in recent studies. Particularly, type I collagen (COL1) expression declines with aging in the leptomeningeal layer of the brain while type IV collagen (COL4) expression is generally steady. This work sought to understand how glucose intake results in the buildup of advanced glycation end-products (AGEs) on the aged brain surface, which causes remodeling of the meningeal matrix made mostly of COL1. According to the study, the aging brain surface accumulates AGEs as a result of repeated sugar intake, which causes the meningeal matrix to change. The decrease in collagen production and rise in collagen breakdown in meningeal fibroblast cells as a result of glycation is what causes this remodeling. Meningeal fibroblast cells subsequently suffer decreased COL1 production and alterations in matrix binding proteins as a result of adapting to the dense collagen membrane. In response to decreased COL1 synthesis, it was shown that DDR2, a receptor tyrosine kinase (RTK), is activated during contacts between meningeal fibroblast cells and the ECM rather than via integrins as is typically thought to happen. It is essential to comprehend how meningeal fibroblast cells contribute to pathogenic alterations in the pial membrane by altering the meningeal matrix. Thus, the study provides insight into the molecular dynamic changes that occur across the surface of the brain, especially in fibroblast cells that have evolved to survive in a glycation-induced environment. These discoveries deepen our comprehension of the intricate interaction between meningeal fibroblast cells, matrix remodeling, and aging. Furthermore, results have larger implications for present and future investigations as well as the design of therapeutic approaches focusing on fibroblast cells and the meningeal matrix to address age-related alterations in the brain.