xenin-25 and Encephalitis

To demarcate pathological events in the brain as a result of short-term to chronic high-fat-diet (HFD) feeding, which leads to cognitive impairment and neuroinflammation, and to assess the efficacy of Xenin-25[Lys(13)PAL] in chronic HFD-fed mice.. C57BL/6 mice were fed an HFD or a normal diet for 18 days, 34 days, 10 and 21 weeks. Cognition was assessed using novel object recognition and the Morris water maze. Markers of insulin signalling and inflammation were measured in brain and plasma using immunohistochemistry, quantitative PCR and multi-array technology. Xenin-25[Lys(13)PAL] was also administered for 5 weeks in chronic HFD-fed mice to assess therapeutic potential at a pathological stage.. Recognition memory was consistently impaired in HFD-fed mice and spatial learning was impaired in 18-day and 21-week HFD-fed mice. Gliosis, oxidative stress and IRS-1 pSer. HFD feeding modulates cognitive function, synapse density, inflammation and insulin resistance in the brain. Xenin-25[Lys(13)PAL] ameliorated markers of inflammation and insulin signalling dysregulation and may have therapeutic potential in the treatment of diseases associated with neuroinflammation or perturbed insulin signalling in the brain.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Behavior, Animal; Biomarkers; Brain; Cognition Disorders; Diet, High-Fat; Disease Models, Animal; Encephalitis; Exploratory Behavior; Gene Expression Regulation, Developmental; Immunohistochemistry; Insulin Resistance; Male; Maze Learning; Mice, Inbred C57BL; Nerve Tissue Proteins; Neurons; Neurotensin; Nootropic Agents; Oxidative Stress; Peptides; Random Allocation