Eicosanoyl-5-hydroxytryptamide (EHT) prevents Alzheimer's disease-related cognitive and electrophysiological impairments in mice exposed to elevated concentrations of oligomeric beta-amyloid.

TitleEicosanoyl-5-hydroxytryptamide (EHT) prevents Alzheimer's disease-related cognitive and electrophysiological impairments in mice exposed to elevated concentrations of oligomeric beta-amyloid.
Publication TypeJournal Article
Year of Publication2017
AuthorsAsam, K, Staniszewski, A, Zhang, H, Melideo, SL, Mazzeo, A, Voronkov, M, Huber, KL, Pérez, E, Stock, M, Stock, JB, Arancio, O, Nicholls, RE
JournalPLoS One
Volume12
Issue12
Paginatione0189413
Date Published2017
ISSN1932-6203
KeywordsAlzheimer Disease, Amyloid beta-Peptides, Animals, Coffee, Cognition, Cognition Disorders, Conditioning (Psychology), Disease Models, Animal, Electrophysiology, Fear, Female, Long-Term Potentiation, Male, Maze Learning, Methylation, Mice, Mice, Inbred C57BL, Nervous System Diseases, Neuronal Plasticity, Phosphorylation, Serotonin, Solubility
Abstract

Soluble forms of oligomeric beta-amyloid (Aβ) are thought to play a central role in Alzheimer's disease (AD). Transgenic manipulation of methylation of the serine/threonine protein phosphatase, PP2A, was recently shown to alter the sensitivity of mice to AD-related impairments resulting from acute exposure to elevated levels of Aβ. In addition, eicosanoyl-5-hydroxytryptamide (EHT), a naturally occurring component from coffee beans that modulates PP2A methylation, was shown to confer therapeutic benefits in rodent models of AD and Parkinson's disease. Here, we tested the hypothesis that EHT protects animals from the pathological effects of exposure to elevated levels of soluble oligomeric Aβ. We treated mice with EHT-containing food at two different doses and assessed the sensitivity of these animals to Aβ-induced behavioral and electrophysiological impairments. We found that EHT administration protected animals from Aβ-induced cognitive impairments in both a radial-arm water maze and contextual fear conditioning task. We also found that both chronic and acute EHT administration prevented Aβ-induced impairments in long-term potentiation. These data add to the accumulating evidence suggesting that interventions with pharmacological agents, such as EHT, that target PP2A activity may be therapeutically beneficial for AD and other neurological conditions.

DOI10.1371/journal.pone.0189413
Alternate JournalPLoS ONE
PubMed ID29253878
PubMed Central IDPMC5734769