Comparing levetiracetam and zonisamide effects on rivastigmine anti-Alzheimer’s activity in aluminum chloride-induced Alzheimer’s-like disease in rats: Impact on α7 nicotinic acetylcholine receptors and amyloid β

Abstract

Background and aim

Alzheimer’s disease (AD) is the most progressive form of neurodegenerative disease, which severely impairs cognitive function. The leading class of drugs used to treat AD is acetylcholinesterase inhibitors (AChE-Is) as Rivastigmine (RIVA), partially ameliorate its cognitive symptoms. Since epilepsy is a common comorbidity with AD, we explored the potential that new the antiepileptic drugs; Levetiracetam (LEV) and Zonisamide (ZNS) may possess an additional therapeutic benefit to RIVA in AlCl₃-induced AD rat model.

Materials and methods

AlCl₃ was used to provoke AD in rats which were then supplemented with treatment drugs for 2 weeks. Treated groups were: Control, AlCl₃, RIVA, LEV, RIVA + LEV, ZNS and RIVA + ZNS. Then, the behavioral tests; passive avoidance (PA), Morris water maze (MWM) and novel object recognition (NOR) were conducted to assess cognitive behavior and memory. The Hippocampal Aβ assembly was thoroughly examined by histopathology and ELISA. α7 Nicotinic ACh receptors’ (α7nAChRs) expression was assessed immunohistochemically and by real-time quantitative polymerase chain reaction (qPCR). Caspase 3 expression was also assessed by real-time qPCR in hippocampal tissues.

Results

AlCl₃ administration impaired memory and cognitive functions in rats, augmented hippocampal Aβ deposition, with subsequent neurodegeneration and α7nAChRs down-regulation. LEV, but not ZNS, administration significantly mitigated AlCl₃-induced cognitive impairment probably through suppression of amyloid β (Aβ) deposition, enhancement of neurogenesis and α7nAChRs expression. When combined to RIVA, ZNS treatment negatively affected cognition possibly through its impact on hippocampal Aβ and subsequent neuronal damage.

Conclusion

Although our results indicated that neither LEV nor ZNS provided any extra benefit to cognitive enhancements in AD rats receiving rivastigmine, LEV demonstrated positive effects individually while ZNS had negative effects when combined with RIVA. As a result, this study suggests the use of LEV rather than ZNS for managing epilepsy in patients with AD given that Alzheimer’s and epilepsy can coexist.