Regulation of Tau protein phosphorylation by glucosamine-induced O-GlcNAcylation as a neuroprotective mechanism in a brain ischemia-reperfusion model.

Tau hyperphosphorylation is a modification frequently observed after brain ischemia which has been related to the aggregation of this protein, with subsequent cytoskeletal damage, and cellular toxicity. The present study tests the hypothesis of using glucosamine, an agent that increases protein O-GlcNAcylation, to decrease the levels of phosphorylation in Tau during ischemia-reperfusion. Transient focal ischemia was artificially induced in male Wistar rats by occlusion of the middle cerebral artery (MCAO) with an intraluminal monofilament. A single dose of intraperitoneal glucosamine of 200 mg/kg diluted in normal saline (SSN) was administered 60 min before ischemia. Histological brain sections were processed using indirect immunofluorescence with primary antibodies (anti-O-GlcNAc and anti pTau-ser 396). The Image J software was used to calculate the immunofluorescence signal intensity. The phosphorylation of Tau at the serine residue 396 had a significant decrease with the administration of glucosamine during ischemia-reperfusion compared with the administration of placebo. These results show that glucosamine can reduce the phosphorylation levels of Tau in rodents subjected to ischemia and cerebral reperfusion, which implies a neuroprotective role of glucosamine.