STC1 ameliorates cognitive impairment and neuroinflammation of Alzheimer’s disease mice via inhibition of ERK1/2 pathway

Abstract

ObjectiveTo investigate the regulatory role of STC1 (Stanniocalcin-1) mediated ERK1/2 pathway in cognitive impairment and neuroinflammation of Alzheimer’s disease (AD). MethodsWT mice and STC1 Tg mice (transgenic overexpression of STC1) were used to establish AD models to perform behavioral test by Morris water maze. Hippocampal cell apoptosis was quantified by TUNEL staining, the levels of inflammatory cytokines in serum and hippocampal tissues determined by ELISA, as well as oxidative stress-related factors detected by corresponding testing kits, and protein expression of STC1 and ERK1/2 pathway measured by Western blotting. ResultsCompared with WT Sham group, WT AD mice had prolonged escape latency, decreased crossing platform times, increased hippocampal cell apoptosis with up-regulated inflammatory cytokines and oxidative stress-related factors, as well as increased STC1 and ERK1/2 pathway-related molecules. By contrast, STC1 Tg AD mice showed shortened escape latency, increased crossing platform times than WT AD mice, and they also exhibited the decreased apoptosis index and inflammatory cytokines, alleviated oxidative stress-injury, down-regulated protein expression of ERK1/2 pathway, and up-regulated the protein expression of STC1 and UCP2. ConclusionSTC1 overexpression could alleviate oxidative stress-induced injury, reduce neuroinflammation, improve cognitive function to play a neuro-protective role by inhibiting ERK1/2 signaling pathway.