Chitosan nanoparticles alleviate Alzheimer’s disease in zebrafish by adopting a dual strategy

Abstract

AbstractBackgroundAlzheimer’s disease (AD) is a progressive neurodegenerative disease. It is the most prevalent form of dementia in the world affecting almost 47 million people worldwide. The main pathological hallmark of AD is progressive memory loss. Zebrafish possess 70% similarity with the human genome. Zebrafish have been used extensively in developmental biology and molecular genetics. Zebrafish are being widely used as a predominant model for studying neurodegenerative diseases. In this current study, we have attempted to establish Aβ induced model of AD in Zebrafish. Validation of this model is done by behavioral analysis.MethodThe various assays performed to test memory were spatial memory testing, preference for light and dark environments and their ability to recognize novel objects from the previous objects. SEM, TEM, FTIR, AFM and particle size analysis were performed to validate the nanoparticles thus formed. Amyloid beta was injected mid ventrally into the zebrafish brain, which were previously given Chrysin by oral gavage.ResultThe various assays performed are spatial memory testing, preference for light and dark environments and their ability to recognize novel objects, which revealed the drastic changes in the behavior of Aβ injected fishes. Further validation of the Aβ model was done using immunohistochemical (IHC) staining of brain sections of Aβ injected fish, which confirmed the presence of Aβ with Aβ antibody. The present study establishes a model of AD in zebrafish which will be useful for therapeutic drug intervention in future. Chitosan nanoparticles loaded with the naturally occurring flavonoid, chrysin, were synthesized. The nanoparticles were validated on the basis of their physical and chemical properties. It was also observed that the chrysin loaded chitosan nanoparticles led to protection and restoration of synapses of the amyloid beta treated zebrafish. Chitosan also possessed the ability to disintegrate the amyloid plaques in vivo. ConclusionThis study provides insight into the dual strategy by which Chrysin‐ Chitosan nanoparticles alleviate Alzheimer’s like condition. This dual strategy adopted by the Chrysin‐ Chitosan nanoparticles therefore holds potential to serve as a therapeutic strategy to treat AD.