Thesis (Ph.D.) - Cairo University - Faculty of Pharmacy - Department of Pharmacology and Toxicology

Since westernized diet-induced insulin resistance is a risk factor in Alzheimer's disease (AD) development and lipopolysaccharide (LPS) coexist with amyloid Ý (AÝ)1-42 in these patients, our novel AD model was developed to resemble sporadic AD by injecting LPS to high fat/fructose diet (HFFD)-fed rats as a source of damage-associated molecular patterns. Our aim was to evaluate the neuroprotective potential of palonosetron, a 5-hydroxytrymptamine (5-HT)-3 antagonist, and the possible involvement of Ü7 nicotinic ACh receptors (nAchR) in palonosetron{u2019}s effects. Animals were allocated into control and HFFD/LPS untreated or treated groups. Palonosetron and/or methyllycaconitine (MLA), Ü7nAchR blocker, were given for 8 days, starting 3 h after LPS and MLA was injected 15 min before each palonosetron dose. All regimens improved histopathological findings and enhanced spatial memory (Morris water maze); however, palonosetron alone or with methyllycaconitine promoted animal performance during novel object recognition test. In the hippocampus, all regimens skewed microglia M1 to M2 phenotype indicated by the decreased M1 markers and the enhanced M2 related parameters

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