Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2018 Aug 13:10:244.
doi: 10.3389/fnagi.2018.00244. eCollection 2018.

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

Neha Atulkumar Singh  1 , Vaishali Bhardwaj  2 , Chandrika Ravi  2 , Nithya Ramesh  2 , Abul Kalam Azad Mandal  2 , Zaved Ahmed Khan  3
Affiliations
Free PMC article

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

Neha Atulkumar Singh et al. Front Aging Neurosci. .
Free PMC article

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.

Keywords: Alzheimer disease; EGCG; aluminum chloride; nanoparticles; neuritic plaques; neurobehavioral impairments; neurofibrillary tangles.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Experiment strategy for aluminum chloride (AlCl3) induction, free epigallocatechin-gallate (EGCG) and EGCG nanoparticle (nanoEGCG) treatment in wistar rats.
Figure 2
Figure 2
Effect of AlCl3 induction, free EGCG and nanoEGCG treatment on (A) Open field test—squares explored, (B) total time immobile, (C) fecal pellets, (D) rearing, (E) Morris water maze—the time taken to escape to the platform, (F) time spent in the target quadrant, (G) Novel object recognition test—discrimination index and (H) recognition index. Abbreviations: C, control; AL, AlCl3 induced Alzheimeric rats; EF, free EGCG treated AlCl3 induced Alzheimeric rats; EN, nanoEGCG treated AlCl3 induced Alzheimeric rats. Significance difference between groups indicated by: * between C and AL, @ between AL and EF and # between AL and EN. Significance levels of p < 0.0001, p < 0.001, p < 0.01 or p < 0.05 are denoted by repetition of these symbols.
Figure 3
Figure 3
Representative histopathology images in the (A) cortex and (B) hippocampus regions of the rat brain (n = 3). Abbreviations: a, neuritic plaques and b, neurofibrillary tangles.
Figure 4
Figure 4
Representative immunohistochemical images in the (A) cortex and (B) hippocampus regions of the rat brain (n = 3). The arrows are indicative of Aβ1–42 levels.
Figure 5
Figure 5
Scoring of the immunohistochemical images in the (A) cortex and (B) hippocampus regions of the rat brain (n = 3). Abbreviations: C, control; AL, AlCl3 induced Alzheimeric rats; EF, free EGCG treated AlCl3 induced Alzheimeric rats; EN, nanoEGCG treated AlCl3 induced Alzheimeric rats. Significance difference between groups indicated by: * between C and AL, @ between AL and EF and # between AL and EN.Significance levels of p < 0.001, p < 0.01 or p < 0.05 are denoted by repetition of these symbols.
Figure 6
Figure 6
Effect of AlCl3 induction, free EGCG and nanoEGCG treatment on (A) Acetylcholinesterase activity, (B) Reactive oxygen species (ROS) generation and (C) Nitric oxide (NO) generation. Abbreviations: C, control; AL, AlCl3 induced Alzheimeric rats; EF, free EGCG treated AlCl3 induced Alzheimeric rats; EN, nanoEGCG treated AlCl3 induced Alzheimeric rats. Significance difference between groups indicated by: * between C and AL, @ between AL and EF and # between AL and EN.Significance levels of p < 0.001, p < 0.01 or p < 0.05 are denoted by repetition of these symbols.
Figure 7
Figure 7
Effect of AlCl3 induction, free EGCG and nanoEGCG treatment on protein level profiles of Aβ1–42, AChE, APP, GSK3β and PDK1 in the (A) hippocampus and (B) cortex regions of the rat brain. Abbreviations: C, control; AL, AlCl3 induced Alzheimeric rats; EF, free EGCG treated AlCl3 induced Alzheimeric rats; EN, nanoEGCG treated AlCl3 induced Alzheimeric rats. Significance difference between groups indicated by: * between C and AL, @ between AL and EF and # between AL and EN.
Figure 8
Figure 8
(A) Plasma and (B) brain concentration of unconjugated EGCG after the oral administration of free EGCG and nanoEGCG.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Ahmed H. H., Shousha W. G., Hussien R. M., Farrag A. R. H. (2011). Potential role of some nutraceuticals in the regression of Alzheimer’s disease in an experimental animal model. Turkish J. Med. Sci. 41, 455–466. 10.3906/sag-0907-136 - DOI
    1. Albert M. S., DeKosky S. T., Dickson D., Dubois B., Feldman H. H., Fox N. C., et al. . (2011). The diagnosis of mild cognitive impairment due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement. 7, 270–279. 10.1016/j.jalz.2011.03.008 - DOI - PMC - PubMed
    1. Amberla K., Nordberg A., Viitanen M., Winblad B. (1993). Long-term treatment with tacrine (THA) in Alzheimer’s disease—evaluation of neuropsychological data. Acta Neurol. Scand. 88, 55–57. 10.1111/j.1600-0404.1993.tb04257.x - DOI - PubMed
    1. Antunes M., Biala G. (2012). The novel object recognition memory: neurobiology, test procedure, and its modifications. Cogn. Process. 13, 93–110. 10.1007/s10339-011-0430-z - DOI - PMC - PubMed
    1. Bhalla P., Garg M. L., Dhawan D. K. (2010). Protective role of lithium during aluminium-induced neurotoxicity. Neurochem. Int. 56, 256–262. 10.1016/j.neuint.2009.10.009 - DOI - PubMed

LinkOut - more resources