Abstract
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) and rivastigmine, alone and in combination, on the progression of Alzheimer's disease induced by intracerebroventricular administration of streptozotocin and possible anti-inflammatory mechanisms of action. Materials and Methods. Adult male albino rats were divided randomly into five groups: group I acts as control. In group II (Alzheimer's group), Alzheimer's 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's rats received rivastigmine (1.5 mg/kg, s.c.) for a period of 21 days immediately after ICV-STZ injection. Group V (rivastigmine + cholecalciferol) 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's, the ICV-STZ induced significant impairment of memory and declined cognition as manifested by the 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 the control group. All these parameters were significantly improved by rivastigmine alone and in combination with vitamin D3. These results clearly pointed to the pivotal role of rivastigmine and vitamin D3 in STZ induced Alzheimer's in rats by improving inflammatory status. Conclusion. The present study concludes the neuroprotective effect of rivastigmine and vitamin D3 in Alzheimer's disease rats by reducing inflammatory mediators (TNF-α and IL-1β) and amyloid β peptide and improving acetylcholine levels in brain.
Highlights
Alzheimer’s disease (AD) is a common neurodegenerative disease that is characterized by progressive impairment of memory and other cognitive functions leading to complete incapacity and death
It has been observed that increased levels of proinflammatory cytokines, including tumor necrosis factor alpha, interleukin 1B (IL-1B), interleukin 6 (IL-6), and interferon γ (IFN-γ), may suspend phagocytosis of amyloid amyloid β (Aβ) in brains of patients with AD [41]
The present study aimed at exploring the neuroprotective effects of rivastigmine and vitamin D3 through their anti-inflammatory properties by the analysis of their effects on behavior changes and measurement of serum and brain tumor necrosis factor α (TNF-α), IL-1β, in addition to the estimation of brain acetylcholine, serum, and brain amyloid β levels
Summary
AD is a common neurodegenerative disease that is characterized by progressive impairment of memory and other cognitive functions leading to complete incapacity and death. Group IV (rivastigmine-treated group) Alzheimer’s rats received rivastigmine (1.5 mg/kg, s.c.) for a period of 21 days immediately after ICV-STZ injection. After 21 days of induction of Alzheimer’s, the ICV-STZ induced significant impairment of memory and declined cognition as manifested by the increased latency period in Morris Water Maze test. All these parameters were significantly improved by rivastigmine alone and in combination with vitamin D3 These results clearly pointed to the pivotal role of rivastigmine and vitamin D3 in STZ induced Alzheimer’s in rats by improving inflammatory status. The present study concludes the neuroprotective effect of rivastigmine and vitamin D3 in Alzheimer’s disease rats by reducing inflammatory mediators (TNF-α and IL-1β) and amyloid β peptide and improving acetylcholine levels in brain
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