Subthreshold Concentrations of Melatonin and Galantamine Improves Pathological AD-Hallmarks in Hippocampal Organotypic Cultures

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dc.contributor.authorBuendía, I.
dc.contributor.authorParada, E.
dc.contributor.authorNavarro González De Mesa, Elisa
dc.contributor.authorLeón Martínez, Rafael
dc.contributor.authorNegredo Madrigal, Pilar
dc.contributor.authorEgea Máiquez, Francisco Javier
dc.contributor.authorGarcía López, Manuela
dc.date.accessioned2024-01-16T09:04:28Z
dc.date.available2024-01-16T09:04:28Z
dc.date.issued2015-06-17
dc.description.abstractMelatonin is a neurohormone whose levels are significantly reduced or absent in Alzheimer's disease (AD) patients. In these patients, acetylcholinesterase inhibitors (AChEI) are the major drug class used for their treatment; however, they present unwanted cholinergic side effects and have provided limited efficacy in clinic. Because combination therapy is being extensively used to treat different pathological diseases such as cancer or acquired immune deficiency syndrome, we posed this study to evaluate if melatonin in combination with an AChEI, galantamine, could provide beneficial properties in a novel in vitro model of AD. Thus, we subjected organotypic hippocampal cultures (OHCs) to subtoxic concentrations of β-amyloid (0.5 μM βA) plus okadaic acid (1 nM OA), for 4 days. This treatment increased by 95 % cell death, which was mainly apoptotic as shown by positive TUNEL staining. In addition, the combination of βA/OA increased Thioflavin S aggregates, hyperphosphorylation of Tau, oxidative stress (increased DCFDA fluorescence), and neuroinflammation (increased IL-1β and TNFα). Under these experimental conditions, melatonin (1-1000 nM) and galantamine (10-1000 nM), co-incubated with the toxic stimuli, caused a concentration-dependent neuroprotection; maximal neuroprotective effect was achieved at 1 μM of melatonin and galantamine. Most effective was the finding that combination of sub-effective concentrations of melatonin (1 nM) and galantamine (10 nM) provided a synergic anti-apoptotic effect and reduction of most of the AD-related pathological hallmarks observed in the βA/OA model. Therefore, we suggest that supplementation of melatonin in combination with lower doses of AChEIs could be an interesting strategy for AD patients.
dc.description.departmentDepto. de Bioquímica y Biología Molecular
dc.description.facultyFac. de Medicina
dc.description.refereedTRUE
dc.description.statuspub
dc.identifier.citationBuendia I, Parada E, Navarro E, León R, Negredo P, Egea J, López MG. Subthreshold Concentrations of Melatonin and Galantamine Improves Pathological AD-Hallmarks in Hippocampal Organotypic Cultures. Mol Neurobiol. 2016 Jul;53(5):3338-3348. doi: 10.1007/s12035-015-9272-5
dc.identifier.doi10.1007/s12035-015-9272-5
dc.identifier.issn0893-7648
dc.identifier.issn1559-1182
dc.identifier.officialurlhttps://link.springer.com/article/10.1007/s12035-015-9272-5
dc.identifier.relatedurlhttps://pubmed.ncbi.nlm.nih.gov/26081146/
dc.identifier.urihttps://hdl.handle.net/20.500.14352/93264
dc.journal.titleMolecular Neurobiology
dc.language.isoeng
dc.page.final3348
dc.page.initial3338
dc.publisherSpringer
dc.rights.accessRightsrestricted access
dc.subject.cdu616.894
dc.subject.keywordAlzheimer disease
dc.subject.keywordCombined therapy
dc.subject.keywordGalantamine
dc.subject.keywordInflammation
dc.subject.keywordMelatonin
dc.subject.keywordOxidative stress
dc.subject.ucmCiencias Biomédicas
dc.subject.unesco24 Ciencias de la Vida
dc.titleSubthreshold Concentrations of Melatonin and Galantamine Improves Pathological AD-Hallmarks in Hippocampal Organotypic Cultures
dc.typejournal article
dc.type.hasVersionVoR
dc.volume.number53
dspace.entity.typePublication
relation.isAuthorOfPublicationd0e22d4d-2011-4a9f-bd9c-609855dba391
relation.isAuthorOfPublication7093c6ce-e368-44f0-a993-8f7212cb1c2a
relation.isAuthorOfPublication.latestForDiscovery7093c6ce-e368-44f0-a993-8f7212cb1c2a
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