Optimizing predictive biomarkers for alzheimer's disease: muscarinic M1 antagonist-induced synaptic signaling disruptions and bee venom intervention through cholinergic modulation and multiregression dose selection.

Abstract

Alzheimer's (AD) is a progressive neurodegenerative disorder characterized by cognitive decline and neurochemical imbalances. The present study aims to ensure the correct dosage of scopolamine (SC) for inducing AD using Quality by Design to optimize the predictive biomarker acetylcholine esterase. Further, neuroprotective effects will be assessed with variable doses of bee venom (BV) by analyzing its effect on cognitive function, neurochemical markers, and oxidative stress. The goal of this study is to improve models of AD and learn more about how BV can protect neurons in a dose-dependent way during treatment. Methods: The rats were randomly divided into six groups (n = 6): Control, SC -induced AD, SC + Memantine (1 mg/kg bwt p.o.), and three BV doses (5, 10, 15 µl/kg, i.p, every other day) to study dose-dependent effects combined with SC. Memantine and BV were given to the animals two months before they developed AD, which happened on its own 14 days after treatment. After four days of behavioral assessment using the Morris Water Maze to evaluate cognitive function, the animals were humanely sacrificed. Blood and brain samples were collected for the measurement of serum liver and kidney function markers, oxidative and nitrosative stress parameters, cellular energy metabolites, amino acid profiles, neurotransmitters, and inflammatory markers in brain tissue. Results and Conclusion: The most remarkable neuroprotective effect was found in the group treated with BV medium and high dose showed a plateau, beyond which no more improvement was shown. These findings point toward a promising therapeutic approach for BV in the cognitive decline of AD.