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Avenanthramide-C Restores Impaired Plasticity and Cognition in Alzheimer's Disease Model Mice

Avenanthramide-C Restores Impaired Plasticity and Cognition in Alzheimer's Disease Model Mice

Vijay Sankar Ramasamy, Manikandan Samidurai, Hyung Joon Park, Ming Wang, Ra Young Park, Seon Young Yu, Hee Kyung Kang, Semi Hong, Won-Seok Choi, Yu Young Lee, Hyung-Seok Kim, Jihoon Jo

Mol Neurobiol. 2020 Jan;57(1):315-330.

PMID: 31332763

Abstract:

Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by cognitive decline and dementia with no effective treatment. Here, we investigated a novel compound from oats named avenanthramide-C (Avn-C), on AD-related memory impairment and behavioral deficits in transgenic mouse models. Acute hippocampal slices of wild-type or AD transgenic mice were treated with Avn-C in the presence or absence of oligomeric Aβ42. LTP analyses and immunoblotting were performed to assess the effect of Avn-C on Aβ-induced memory impairment. To further investigate the effect of Avn-C on impaired memory and Aβ pathology, two different AD transgenic mice (Tg2576 and 5XFAD) models were orally treated with either Avn-C or vehicle for 2 weeks. They were then assessed for the effect of the treatment on neuropathologies and behavioral impairments. Avn-C reversed impaired LTP in both ex vivo- and in vivo-treated AD mice hippocampus. Oral administration (6 mg/kg per day) for 2 weeks in AD mice leads to improved recognition and spatial memory, reduced caspase-3 cleavage, reversed neuroinflammation, and to accelerated glycogen synthase kinase-3β (pS9GSK-3β) and interleukin (IL-10) levels. Avn-C exerts its beneficial effects by binding to α1A adrenergic receptors to stimulate adenosine monophosphate-activated kinase (AMPK). All of the beneficial effects of Avn-C on LTP retrieval could be blocked by prazosin hydrochloride, a specific inhibitor of α1A adrenergic receptors. Our findings provide evidence, for the first time, that oats' Avn-C reverses the AD-related memory and behavioral impairments, and establish it as a potential candidate for Alzheimer's disease drug development.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP116764159	Avenanthramide C		116764-15-9	Price

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