The possible effects of different therapeutic approaches on experimentally induced model of Alzheimer{u2019}s disease / Rofida Abdalla Saleh Hamed ; Supervised Sanaa A. Kenawy , Amina S. Attia , Noha F. Hamed

Thesis (M.Sc.) - Cairo University - Faculty of Pharmacy - Department of Pharmacology and Toxicology

Alzheimer's disease (AD), the most common form of dementia, is characterized by the loss of normal functions of brain cells and neuronal death, ultimately leading to memory loss. The current study was directed to investigate the possible neuroprotective effects of saxagliptin and pentoxifylline, alone or in combination against scopolamine-induced Alzheimer-like pathology in adult male rats. Oral administration of saxagliptin (3 mg/kg) and a combination regimen of saxagliptin and pentoxifylline (30mg/kg) mitigated scopolamine-induced cognitive and spatial memory deficits in rats. Such effects were accentuated by the associated increase in hippocampal acetylcholine content and a reduction in Ý-amyloid plaques, tau phosphorylation and its upstream glycogen synthase kinase 3-Ý (GSK-3Ý) contents. Moreover, saxagliptin and the combination regimen restored scopolamine-induced impairment of neuronal insulin verified by increased serum and hippocampal insulin, GLP-1 and CREB contents. This was associated with a decrease in TNF-Ü and caspase-3 contents in hippocampal tissues. However, oral administration of pentoxifylline alone restored neither the cholinergic system nor the insulin signaling pathway, whereas it significantly reduced hippocampal TNF- Ü and caspase-3 contents along with increased hippocampal CREB content

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