Resveratrol differentially affects MMP ‐9 release from neurons and glia; implications for therapeutic efficacy

“Resveratrol has differential effects on neuronal and glial MMP release” As shown above, resveratrol inhibits basal and LPS-stimulated release of MMP2/9 from cultured glia, which may promote BBB injury, but spares basal and NMDA-stimulated MMP-9 release from neurons, which may promote neuronal p lasticity. Of interest, however, resveratrol reduces PNN component expression from both culture types. AbstractResveratrol, a naturally occurring polyphenol that activates sirtuin 1 (SIRT1), has been shown to reduce overall levels of matrix metalloprotease-9 (MMP-9) in cerebrospinal fluid (CSF) samples from patients with Alzheimer's dementia (AD). Depending on the site of release, however, MMP-9 has the potential to improve or impair cognition. In particular, its release from microglia or pericytes proximal to the blood brain barrier can damage the basement membrane, while neuronal activity-dependent release of this protease from glutamatergic neurons can instead promote dendritic spine expansion and long-term potentiation of synaptic plasticity. In the present study, we test the hypothesis that resveratrol reduces overall MMP-9 levels in CSF samples from patients with APOE4, an allele associated with increased glial inflammation. We also examine the possibility that resveratrol reduces inflammation-associated MMP release from cultured glia but spares neuronal activity-dependent release from cultured cortical neurons. We observe that resveratrol decreases overall levels of MMP-2 a...
Source: Journal of Neurochemistry - Category: Neuroscience Authors: Tags: ORIGINAL ARTICLE Source Type: research