title: Subclinical Doses of ATP-Sensitive Potassium Channel Modulators Prevent Alterations in Memory and Synaptic Plasticity Induced by Amyloid-β.
abstract: In addition to coupling cell metabolism and excitability, ATP-sensitive potassium channels (KATP) are involved in neural function and plasticity. Moreover, alterations in KATP activity and expression have been observed in Alzheimer's disease (AD) and during amyloid-β (Aβ)-induced pathology. Thus, we tested whether KATP modulators can influence Aβ-induced deleterious effects on memory, hippocampal network function, and plasticity. We found that treating animals with subclinical doses (those that did not change glycemia) of a KATP blocker (Tolbutamide) or a KATP opener (Diazoxide) differentially restrained Aβ-induced memory deficit, hippocampal network activity inhibition, and long-term synaptic plasticity unbalance (i.e., inhibition of LTP and promotion of LTD). We found that the protective effect of Tolbutamide against Aβ-induced memory deficit was strong and correlated with the reestablishment of synaptic plasticity balance, whereas Diazoxide treatment produced a mild protection against Aβ-induced memory deficit, which was not related to a complete reestablishment of synaptic plasticity balance. Interestingly, treatment with both KATP modulators renders the hippocampus resistant to Aβ-induced inhibition of hippocampal network activity. These findings indicate that KATP are involved in Aβ-induced pathology and they heighten the potential role of KATP modulation as a plausible therapeutic strategy against AD.
authors.affiliation: Departamento de Neurobiología del Desarrollo y Neurofisiología, Instituto de Neurobiología, Universidad Nacional Autónoma de México, Querétaro, QRO, México.
authors.forename: Karla
authors.initials: K
authors.lastname: Salgado-Puga
authors.affiliation: Departamento de Neurobiología del Desarrollo y Neurofisiología, Instituto de Neurobiología, Universidad Nacional Autónoma de México, Querétaro, QRO, México.
authors.forename: Javier
authors.initials: J
authors.lastname: Rodríguez-Colorado
authors.affiliation: Departamento de Neurobiología Conductual y Cognitiva, Instituto de Neurobiología, Universidad Nacional Autónoma de México, Querétaro, QRO, México.
authors.forename: Roberto A
authors.initials: RA
authors.lastname: Prado-Alcalá
authors.affiliation: Departamento de Neurobiología del Desarrollo y Neurofisiología, Instituto de Neurobiología, Universidad Nacional Autónoma de México, Querétaro, QRO, México.
authors.forename: Fernando
authors.initials: F
authors.lastname: Peña-Ortega
mesh_terms: D016229:Amyloid beta-Peptides; D000818:Animals; D003981:Diazoxide / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D054086:KATP Channels / Q000378:metabolism; D008297:Male; D049990:Membrane Transport Modulators / Q000494:pharmacology; D008569:Memory Disorders / Q000378:metabolism / Q000517:prevention & control*; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009473:Neuronal Plasticity / Q000187:drug effects* / Q000502:physiology; D018697:Nootropic Agents / Q000494:pharmacology*; D010446:Peptide Fragments; D017208:Rats, Wistar; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D046509:Tissue Culture Techniques; D014044:Tolbutamide / Q000494:pharmacology*
chemical_list: D016229:Amyloid beta-Peptides; D054086:KATP Channels; D049990:Membrane Transport Modulators; D018697:Nootropic Agents; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D014044:Tolbutamide; D003981:Diazoxide
keywords: Amyloid-β protein; burrowing; hippocampal population activity; learning and memory; long-term depression; long-term potentiation; sulphonylurea