Liraglutide improves cognitive outcome of diabetic sepsis-surviving 4 rats; possible involvement of tumor necrosis factor alpha and 5 hippocampal synaptic markers

Diabetes mellitus and sepsis are major causes of cognitive decline. Liraglutide (LIRA) is a GLP-1 agonist with potential beneficial effects on the CNS. The purpose of our study is to investigate the possible effect of liraglutide on post-sepsis cognitive decline in diabetic rats. Male albino rats were divided into five groups: Control group (C), Diabetes group (D), Diabetic-Septic group (DS), Diabetes-Sepsis LIRA-treated group (DS-ttt), Diabetic-septic pretreated group (DS-pre). After sepsis induction, DS-pre group showed significantly higher survival rate in comparison to DS and DS-ttt groups. At the end of experimental period, cognitive tests; (Y-maze) and Novel Object Recognition (NOR) test revealed significantly decreased percentage of correct alternations and discrimination index (DI), respectively, in D and DS groups and a significant increase in the LIRA treated groups (DS-ttt) and (DS-pre). In the hippocampus, inflammatory marker (TNF- α) increased, while synaptic function markers (CREB) and synaptophysin decreased significantly in D and DS groups. In these groups multiple degenerative changes in all hippocampal regions were found on H & E staining. LIRA treatment improved all these abnormalities. In conclusion, these findings suggest a possible role of LIRA in improvement of cognitive function in diabetic rats surviving sepsis; this effect could be mediated via modulation of inflammatory markers, insulin signaling in the hippocampus, synaptic function alteration, and microglial or astrocytic cells changes.