AbstractBackgroundIntracerebroventricular (icv) application of streptozotocin (STZ) causes mytochondrial dysfunction, oxidative stress and other metabolic effects, which leads to accumulation of τ‐protein and Aß plaques that makes it suitable for animal model of sporadic Alzheimer’s disease (sAD). We aimed to explore whether acute effect of single oral galactose dose is mediated by glucagon‐like peptide‐1 (GLP‐1) in sAD rat model.MethodWistar rats were injected icv with STZ (3 mg/kg) or vehicle only (CTR). One month after the injection, animals were divided into three experiments. First experiment: 200 mg/kg galactose was given orally and CTR animals were sacrificed 30, 60 and 120 min after administration. Second experiment: GLP‐1R antagonist (Exendin 9‐39, 85 µg/kg; GLP1Ra) was administered icv in both groups and animals were sacrificed 30 min after the injection. Third experiment: 30 min prior to oral galactose, rats were injected icv with GLP‐1Ra, and animals were sacrificed 120 min after galactose load. PDH, COXIV, CytC and Casp‐3 levels were measured by Western blot method and lactate, ATP and SOD were measured by ELISA in HPT. Glucose, galactose and GLP‐1 levels were measured in plasma and CSF. Data were analyzed by principal component analysis and Spearman rank correlation.ResultMetabolic changes were found more pronounced 120 min after single galactose load: reduced levels of Casp‐3 and PDH and increased SOD levels in HPT; increased CSF glucose. GLP1Ra decreased the levels of lactate, COXIV and CytC and increased PDH and Casp‐3 levels in HPT, only in STZ treated animals. CytC was found negatively correlated with ATP and PDH levels in HPT. GLP1Ra decreased the levels of CytC and SOD and increased PDH levels in CTR only after oral galactose.ConclusionGLP1Ra might inhibit decreased PDH levels caused by single galactose load. GLP1R central inhibition has more pronounced effect in STZ‐icv treated rats suggesting the involvement of GLP1 signaling in model pathogenesis. Supported by Croatian Science Foundation and co‐financed by the Scientific Centre of Excellence for Basic, Clinical and Translational Neuroscience (project “Experimental and clinical research of hypoxic‐ischemic damage in perinatal and adult brain”; GA KK01.1.1.01.0007 funded by the European Union through the European Regional Development Fund).
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