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

Autor: Ramasamy, Vijay Sankar, Samidurai, Manikandan, Park, Hyung Joon, Wang, Ming, Park, Ra Young, Yu, Seon Young, Kang, Hee Kyung, Hong, Semi, Choi, Won-Seok, Lee, Yu Young, Kim, Hyung-Seok, Jo, Jihoon
Zdroj: Molecular Neurobiology; Jan2020, Vol. 57 Issue 1, p315-330, 16p
Abstrakt: 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. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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