Background: Alzheimer’s disease (AD) is a multifactorial disease and the mechanisms underlying its pathogenesis are complex. Several studies have implicated amyloid β (Aβ) accumulation, hyperphosphorylated tau, oxidative stress, metal dysregulation, mitochondrial dysfunction, and inflammatory response as major interconnecting networks leading to neuronal and synaptic degeneration.
Aim The present study was designed to evaluate the neuroprotective effects of cholecalciferol (vitamin D3), rivastigmine alone and in combination on the progression of Alzheimer disease induced by intracerebroventricular administration of streptozotocin and possible anti-inflammatory mechanism of action.
Material and methods: adult male albino rats were divided randomly into five groups; group I act as control. In group II (Alzheimer group) Alzheimer was induced by single bilateral intracerebroventricular injection of STZ (3mg/kg). Group III (cholecalciferol treated group) rats received cholecalciferol (42 IU/kg, s.c.) for 21 days immediately after ICV-STZ injection. Group IV (rivastigmine-treated group) Alzheimer rats received rivastigmine (1.5 mg/kg, s.c) for a period of 21 days immediately after ICV-STZ injection. Group V (rivastigmine + cholecalciferol) group rats received rivastigmine plus cholecalciferol for 21 days immediately after ICV-STZ injection. Cognitive impairment was evaluated by Morris Water Maze test, serum and brain pro-inflammatory mediators (TNF-α and IL-1β) were measured. Also, brain level of acetylcholine was measured. Moreover, serum and brain levels of amyloid beta peptide were evaluated.
Results: after 21 days of induction of Alzheimer, the ICV-STZ induced significant impairment of memory and decline cognition as manifested by increased latency period in Morris Water Maze test. Serum and brain levels of TNF-α, IL-1β and amyloid peptide were significantly increased. On the other hand, brain acetylcholine level was significantly decreased compared with control group. All these parameters were significantly improved by rivastigmine alone and in combination with vitamin D3. These results clearly pointed the pivotal role of rivastigmine and vitamin D3 in STZ induced Alzheimer in rats by improving inflammatory status.
Conclusion: The present study concludes the neuroprotective effect of rivastigmine and vitamin D3 in Alzheimer disease rats by reducing inflammatory mediators (TNF-α and IL-1β), amyloid β peptide and improving acetylcholine levels in brain.
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