Increasing O-GlcNAcylation is neuroprotective in young and aged brains after ischemic stroke.

In this study, using transient ischemic stroke models, we first demonstrated that neuron-specific overexpression of Xbp1s improved outcome, and pharmacologically boosting O-GlcNAcylation with thiamet-G reversed worse outcome observed in neuron-specific Xbp1 knockout mice. We further showed that thiamet-G treatment improved long-term functional recovery in both young and aged animals after transient ischemic stroke. Mechanistically, using an analytic approach developed here, we discovered that availability of UDP-GlcNAc was compromised in the aged brain, which may constitute a novel mechanism responsible for the impaired O-GlcNAcylation activation in the aged brain after ischemia. Finally, based on this new mechanistic finding, we evaluated and confirmed the therapeutic effects of glucosamine treatment in young and aged animals using both transient and permanent stroke models. Our data together support that increasing O-GlcNAcylation is a promising strategy in stroke therapy.
PMID: 33600817 [PubMed - as supplied by publisher]

Source: Experimental Neurology - February 15, 2021 Category: Neurology Authors: Wang Z, Li X, Spasojevic I, Lu L, Shen Y, Qu X, Hoffmann U, Warner DS, Paschen W, Sheng H, Yang W Tags: Exp Neurol Source Type: research