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P2‐155: NEUROMODULATORY ROLE OF CHEBULINIC ACID IN THE DEVELOPMENT OF β AMYLOID OLIGOMER‐INDUCED EXPERIMENTAL DEMENTIA IN RATS
Author(s) -
Arora Rimpi
Publication year - 2019
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2019.06.2562
Subject(s) - oxidative stress , medicine , neuroprotection , endocrinology , hippocampus , dementia , neurotoxicity , hippocampal formation , amyloid (mycology) , pathology , disease , toxicity
Background: Alzheimer’s disease (AD) is the most common cause of dementia in the elderly. The main hallmarks of this disease include progressive cognitive dysfunction and an accumulation of soluble oligomers of b-amyloid (Ab) 1-42 peptide. Chebulinic acid (ChA) has been reported to possess neuroprotective potential in various neurodegenerative models such as anxiety and depression.Methods: In the current study, the ChAwas challenged against intracerebroventricular (ICV)b-amyloid (Ab) -induced neurotoxicity to determine its therapeutic potential in dementia. b-amyloid (Ab) was infused bilaterally (3nmol/3 mL/icv) on day 1 and 3 after surgery. ChA (25, 50 and 100mg/kg/p.o) was administered from 7 day onwards up to 21 day following 1 ICVb-amyloid (Ab) infusion. Spatial and non-spatial memory was evaluated and terminally the animals were sacrificed and hipoocampal brain regions were used to identify biochemical and histopathologicsal alterations. Results: Ventricular administration of b-amyloid (Ab) in rats caused impairment in learning and memory indicating cognitive dysfunctions. The observed cognitive dysfunctions was also associated with significant alterations in hippocampal biochemistry, including elevation in oxidative stress, found to significantly shorten the latency time on the MWM and ORTwhich was associated with increase in oxidative stress (lipid peroxidation and nitrite), compromised antioxidant defense (reduced glutathione), neurotransmitter alteration (AChE, dopamine, noradrenaline, 5-hydoxytryptamine, Gama amino butyric acid and glutamate) and elevation in neuroinflammatory cytokine (IL-1 b, IL-6 and TNFa) levels. The number of apoptotic neurons was increased in hippocampus tissue after ICVAb administration. The histopathological studies in the brain of rats also supported that ChAmarkedly reduced the ICV-Ab -induced histopathological changes and well preserved the normal histological architecture of the hippocampus. The study demonstrates the effectiveness of ChA, as a powerful antioxidant, anti-inflammatory and neuromodulatory in preventing the all these detrimental effects induced by Ab. Conclusions: ChA treatment significantly prevented the ICVAb -induced memory deficit by attenuating the hippocampal neuronal loss, neuroinflammation and compromised antioxidant defense and cholinergic deficit in rats. Thus, ChA may have a therapeutic value for the treatment of AD.