metformin protective effects in lps-induced alzheimer's disease mice model: no-cgmp-katp pathway involvement

This project has studied the effects of metformin on cognition impairment, depression, hyperalgesia, stress oxidative and neuroinflammation in a rodent alzheimer's disease (ad) model created via lps (lipopolysaccharide). for defining possible mechanisms, the no/cgmp/katp pathway roleplay was considered.  mice model was created via lps treatment. open field forced swimming and hot plate tests were done. shuttle-box test and y-maze test were used to assay learning-memory. biochemical assay compromised malondialdehyde (mda) and tnf-alpha concentration and superoxide dismutase (sod) activity measurement in hippocampus samples. no-cgmp-katp pathway contribution was assessed by its agonists/antagonist pre-treatment, 15 min before metformin (150, 200, 250 mg/kg). initial latency (il) was increased by lps injection while it was reduced by metformin (250 mg), in shuttle-box test. pretreatment with methylene blue, l-name and glibenclamide before metformin augmented il, although it was diminished by l- arginine and sildenafil pretreatment. also, metformin increased the lps induced step through latency (stl) reduction. l-name, methylene blue and glibenclamide decreased the stl, but it was increased by l-arginine and sildenafil. in y-maze test, metformin increased the lps-induced spontaneous alternation reduction. l-name, methylene blue and glibenclamide decreased it. lps added immobility time in forced swimming trial, whereas it was reduced thru metformin. l-name, methylene blue and glibenclamide increased the anti-depressive effect of metformin while it was attenuated via l-arginine, sildenafil and diazoxide. lps treatment diminished the threshold of pain perception in hot-plate test, while metformin didn’t have any significant effect. metformin reduced the lps-induced lipid peroxidation (mda level). but, l-name, methylene blue and glibenclamide worsen the lipid peroxidation, whereas it was improved by l-arginine and sildenafil. metformin improved lps-induced reduction in sod activity. sod activity was reduced by l-name, methylene blue and glibenclamide pre-treatment. lps enhanced tnf-alpha amount that decreased by metformin. pre-injection with methylene blue, l-name and glibenclamide increased tnf-alpha concentrations while l-arginine, sildenafil and diazoxide reduced it. conclusions: metformin can improve learning-memory loss, depression, hyperalgesia, neuroinflammation and oxidative stress produced by lps and no/cgmp/katp pathway maybe has a roleplay.