| Summary: | 碩士 === 國立臺灣師範大學 === 生物學系 === 99 === Hyperglycemia is a main characteristic of diabetes mellitus (DM) pathology and has been linked to increased risk of cognitive impairment and dementia. However, the priming effects of the hyperglycemia in inflammation are still unclear. Chronic hyperglycemia was induced in male C57BL/6J mice to mimic DM by intraperitoneal injection of streptozotocin (STZ), which specifically destroys pancreatic β-islet cells. Ten days after STZ treatment, intrahippocampal infusion of vehicle or lipopolysaccharides (LPS) was given to these hyperglycemic/normoglycemic mice. We then examined the cognitive function and molecular alteration of these mice. Severe impairment of the aversive memory and spatial learning acquisition was induced by LPS in hyperglycemic mice via unbalance of the serotonergic and noradrenergic system. Furthermore, the spatial learning and memory was correlated inflammatory response (COX1, COX2, CD45), Aβ1-42, NF-κB, and cognitive related neurotransmitters’ deficit. Exendin-4 (EX-4) is a glucagon-like peptide-1 receptor (GLP-1R) agonist, Evidences suggest that EX-4 could cross the blood brain barrier and attenuate the cellular toxicity in the Alzheimer’s disease or Parkinson’s disease. In this study, we showed that EX-4 treatment improved spatial and aversive learning and memory in intrahippocampal LPS injection or/and hyperglycemic mice. In summary, EX-4 might be considered as potential adjuvant entity for preventing neurodegerative diseases.
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