Glucosamine and Tau protein phosphorylation in a brain permanent-ischemia animal model: a paradoxical effect? (P3-5.006)

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<h3>Objective:</h3> The aim is to establish if glucosamine administration reduces the levels of Tau phosphorylation in an animal model of permanent ischemia. <h3>Background:</h3> Thrombolysis and thrombectomy) are the main treatments for stroke. However, a significant number of patients are not eligible for these treatments. Alternative managements are necessary to reduce post-stroke consequences (PSC). The aggregation of hyperphosphorylated Tau (P-Tau) is observed after brain ischemia which leads to PSC. Glucosamine has demonstrated positive effects on stroke and controversial effects over Tau. <h3>Design/Methods:</h3> Twelve male Wistar rats were included. Focal ischemia (six hours) without reperfusion induced by occlusion of the middle cerebral artery (MCAO) with an intraluminal monofilament. A single dose of intraperitoneal glucosamine of 200 mg/kg was administered 60 min before ischemia. Control was saline. Histological brain sections were processed using immunofluorescence with primary antibodies (anti-O-GlcNAc and anti-pTau-ser 396). Image J software was used to measure immunofluorescence signal intensity. Descriptive statistics, linear regression, Mann-Whitney test, and Pearson correlation were used. The study was authorized by the ethics committee. <h3>Results:</h3> P-Tau raised significantly under permanent ischemia as well as anti-O-GlcNAc. P-Tau at the serine 396 had a positive correlation with anti-O-GlcNAc (0.33, p: &lt;0001) A significant increase in phosphorylation was observed after glucosamine (coef 9565 p: &lt;0001) (17524 vs 13001 p: &lt;0001). The number of cells was higher in the glucosamine group (358 vs 203). <h3>Conclusions:</h3> O-GlcNAcylation after stroke is protective against brain injury in reperfusion. However, permanent ischemia leads to irreversible changes including Tau hyperphosphorylation which could decrease the neuroprotective effects of O-GlcNAcylation. Glucosamine increased O-GlcNAcylation and P-Tau in our study (a paradoxical reaction). Nonetheless, the glucosamine group had less cell destruction what it may implies that glucosamine exerts neuroprotective effects by other mechanisms. Further investigations are needed. <b>Disclosure:</b> Dr. Quintana has nothing to disclose. Mr. Cardozo has nothing to disclose. Dr. Arango has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Procaps. Dr. Arango has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Lundbeck. Dr. Rengifo has nothing to disclose.