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

Autor: Jihoon Jo, Manikandan Samidurai, Seon Young Yu, Ra Young Park, Hyung-Seok Kim, Hee Kyung Kang, Yu Young Lee, Hyung Joon Park, Won Seok Choi, Vijay Sankar Ramasamy, Semi Hong, Ming Wang
Rok vydání: 2019
Předmět:
0301 basic medicine
Genetically modified mouse
medicine.medical_specialty
Adrenergic receptor
Long-Term Potentiation
Neuroscience (miscellaneous)
Administration
Oral
Mice
Transgenic
Models
Biological
03 medical and health sciences
Cellular and Molecular Neuroscience
0302 clinical medicine
Cognition
Alzheimer Disease
Internal medicine
Receptors
Adrenergic
alpha-1
medicine
Memory impairment
Animals
ortho-Aminobenzoates
Cognitive decline
Glycogen synthase
Neuroinflammation
Spatial Memory
Inflammation
Amyloid beta-Peptides
Neuronal Plasticity
biology
business.industry
Adenylate Kinase
Brain
Long-term potentiation
Recognition
Psychology
Impaired memory
Enzyme Activation
Mice
Inbred C57BL
Disease Models
Animal
030104 developmental biology
Endocrinology
Neurology
biology.protein
business
030217 neurology & neurosurgery
Zdroj: Molecular neurobiology. 57(1)
ISSN: 1559-1182
Popis: 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.
Databáze: OpenAIRE
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