Neuroprotective role of astaxanthin in hippocampal insulin resistance induced by Aβ peptides in animal model of Alzheimer's disease.

Abstract

With the constant failure of the clinical trials continuous exploration of a therapeutic target against Alzheimer's disease (AD) is the utmost need. Numerous studies have supported the hypothesis that central insulin resistance plays a significant role in AD. Serine phosphorylation of Insulin Receptor Substarte-1 (IRS-1) has been found to be a contributing factor in neuronal insulin resistance. Astaxanthin (ASX) is xanthophyll carotenoid which has previously demonstrated significant antidiabetic and neuroprotective actions. In the present study, AD was induced by i.c.v administration of Amyloid-β (1-42) peptides in Wistar rats. After 7 days of recovery, rats were treated with 0.5 mg/kg and 1 mg/kg of ASX orally for 28 days. Behavioral analysis was done in the last week of our experimental study. On the 36th day, rats were sacrificed and their hippocampus were separated from the whole brain, then homogenized and stored for biochemical estimations. ASX significantly and dose-dependently reversed the cognitive and memory impairment, assessed by Morris water maze test and Novel object Recognition test, Aβ (1-42) peptides infused Wistar rats. ASX also significantly attenuated soluble Aβ (1-42) level, IRS-S307 activity, GSK-3β activity, TNF-α level, AChE level, nitrite level and oxidative stress in the hippocampus. Histopathological evaluation, done through H&E and Congo red staining, also demonstrated neuroprotective and anti-amyloidogenic effects of ASX in hippocampus. Our study concludes preventive action of Astaxanthin against hippocampal insulin resistance and Alzheimer's disease complications, supporting potential role of hippocampal insulin resistance targeting against AD.

• Authors: Syed Obaidur Rahman, Bibhu Prasad Panda, Suhel Parvez, Madhu Kaundal, Salman Hussain, Mohd Akhtar, Abul Kalam Najmi
• Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie (Biomed Pharmacother) Vol. 110 Pg. 47-58 (Feb 2019) ISSN: 1950-6007 [Electronic] France
• PMID: 30463045 (Publication Type: Journal Article)
• Copyright: Copyright © 2018 The Authors. Published by Elsevier Masson SAS.. All rights reserved.

Chemical References

• Amyloid beta-Peptides
• Neuroprotective Agents
• Peptide Fragments
• Xanthophylls
• amyloid beta-protein (1-42)
• astaxanthine

Topics

• Alzheimer Disease (chemically induced, metabolism, prevention & control)
• Amyloid beta-Peptides (metabolism, toxicity)
• Animals
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Female
• Hippocampus (drug effects, metabolism)
• Injections, Intraventricular
• Insulin Resistance (physiology)
• Maze Learning (drug effects, physiology)
• Neuroprotective Agents (pharmacology, therapeutic use)
• Peptide Fragments (metabolism, toxicity)
• Random Allocation
• Rats
• Rats, Wistar
• Xanthophylls (pharmacology, therapeutic use)