EGCG Nanoparticles Attenuate Aluminum Chloride Induced Neurobehavioral Deficits, Beta Amyloid and Tau Pathology in a Rat Model of Alzheimer's Disease.

Neha Atulkumar Singh,Vaishali Bhardwaj,Abul Kalam Azad Mandal,Zaved Ahmed Khan,Chandrika Ravi,Nithya Ramesh

doi:10.3389/fnagi.2018.00244

Neha Atulkumar Singh, Vaishali Bhardwaj + Show 4 more

Open Access

https://doi.org/10.3389/fnagi.2018.00244

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Abstract

Rational: Alzheimer’s disease (AD) is a neurodegenerative pathology characterized by the presence of neuritic plaques and neurofibrillary tangles. Aluminum has been reported to play an important role in the etiology and pathogenesis of this disease. Hence, the present study aimed to evaluate the neuroprotective role of epigallocatechin-gallate (EGCG) loaded nanoparticles (nanoEGCG) against aluminum chloride (AlCl3) induced neurobehavioral and pathological changes in AD induced rats.Method: 100 mg/kg body weight AlCl3 was administered orally for 60 days, which was followed by 10 mg/kg body weight free EGCG and nanoEGCG treatment for 30 days. Morris water maze, open field and novel object recognition tests were employed for neurobehavioral assessment of the rats. This was followed by histopathological assessment of the cortex and the hippocampus in the rat brain. For further validation biochemical, immunohistochemistry and western blot assays were carried out.Result: Aluminum exposure reduced the exploratory and locomotor activities in open field and significantly reduced the memory and learning curve of rats in Morris water maze and novel object recognition tests. These neurobehavioral impairments were significantly attenuated in nanoEGCG treated rats. Histopathological assessment of the cortex and hippocampus of AlCl3 induced rat brains showed the presence of both neuritic plaques and neurofibrillary tangles. In nanoEGCG treated rats this pathology was absent. Significant increase in biochemical, immunohistochemical and protein levels was noted in AlCl3 induced rats. While these levels were greatly reduced in nanoEGCG treated rats.Conclusion: In conclusion, this study strengthens the hypothesis that EGCG nanoparticles can reverse memory loss, neuritic plaque and neurofibrillary tangles formation.

Highlights

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that imposes significant economic and social burden on society (Singh et al, 2016)
AD is mainly classified into two forms; sporadic and non-sporadic, where less than 5% cases account for the non-sporadic form and 95% cases account for the sporadic form
NanoEGCG Enhanced Locomotor Activity in Alzheimeric Rats Locomotion and other exploratory behaviors of rats were studied through open field test (Figures 2A,B)

Summary

Introduction

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that imposes significant economic and social burden on society (Singh et al, 2016). The most important biomarkers for AD pathology include phosphorylated tau protein (P-tau) and 1–42 amino acid form of beta amyloid (Aβ42). Of these Aβ42 fibril accumulation is considered to be the instigator of this neurodegenerative pathology and a cascade of events including neurotoxicity, inflammation and oxidative stress (Hardy and Selkoe, 2002). Patients are affected by AD differently, as their experience in symptoms and disease progression is different (Albert et al, 2011). This is mainly due to the difference in factors such as genetics, age, education and co-morbidities (Kim et al, 2002)

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