Reboxetine Treatment Reduces Neuroinflammation and Neurodegeneration in the 5xFAD Mouse Model of Alzheimer's Disease: Role of CCL2

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dc.contributor.authorLópez Gutiérrez, Irene
dc.contributor.authorGarcía Bueno, Borja
dc.contributor.authorCaso Fernández, Javier Rubén
dc.contributor.authorGarcía Bueno, Borja
dc.contributor.authorLeza Cerro, Juan Carlos
dc.contributor.authorMuñoz Madrigal, José Luis
dc.date.accessioned2023-11-21T12:05:43Z
dc.date.available2023-11-21T12:05:43Z
dc.date.issued2019-07-11
dc.description.abstractThe reduction of brain noradrenaline levels is associated to the initiation of Alzheimer’s disease and contributes to its progression. This seems to be due mainly to the anti-neuroinflammatory actions of noradrenaline. The analysis of noradrenaline effects on brain cells demonstrates that it also regulates the production of the chemokine CCL2. In the present study, we analyzed the effect of the selective noradrenaline reuptake inhibitor, reboxetine, on the inflammatory and neurodegenerative alterations present in 5xFAD mice, and how the genetic removal of CCL2 affects reboxetine actions. We observed that the removal of CCL2 reduced the memory impairments in 5xFAD mice as well as the neuroinflammatory response, the accumulation of amyloid beta plaques, and the degeneration of neurons in the brain cortex. The administration of reboxetine with osmotic pumps for 28 days also resulted in anti-inflammatory and neuroprotective changes in 5xFAD mice, even in the absence of CCL2. Yet, 6-month-old CCL2KO mice presented a significant degree of neuroinflammation and neuronal damage. These findings indicate that reboxetine treatment prevents the brain alterations caused by prolonged overproduction of amyloid beta, being these effects independent of CCL2, which is a mediator of the damage caused by amyloid beta in the brain cortex, but necessary for the prevention of the development of neurodegeneration in normal healthy conditions.
dc.description.departmentDepto. de Farmacología y Toxicología
dc.description.facultyFac. de Medicina
dc.description.refereedTRUE
dc.description.sponsorshipUniversidad Complutense de Madrid
dc.description.sponsorshipSpanish Ministry of Science
dc.description.sponsorshipCentro de Investigación Biomédica en Red de Salud Mental (CIBERSAM)
dc.description.sponsorshipEuropean Youth Employment Initiative (YEI)
dc.description.statuspub
dc.identifier.doi10.1007/s12035-019-01695-6
dc.identifier.issn0893-7648
dc.identifier.relatedurlhttps://www.springer.com/journal/12035
dc.identifier.urihttps://hdl.handle.net/20.500.14352/88880
dc.issue.number12
dc.journal.titleMolecular Neurobiology
dc.language.isoeng
dc.page.final8642
dc.page.initial8628
dc.publisherSpringer
dc.relation.projectIDPR26/16-20278
dc.relation.projectIDSAF2017-86620-R
dc.rights.accessRightsrestricted access
dc.subject.cdu616.894-053.9
dc.subject.keywordNoradrenaline
dc.subject.keywordReboxetine
dc.subject.keywordCCL2
dc.subject.keywordMCP-1
dc.subject.keyword5xFAD
dc.subject.keywordNeuroinflammation
dc.subject.ucmCiencias Biomédicas
dc.subject.unesco32 Ciencias Médicas
dc.titleReboxetine Treatment Reduces Neuroinflammation and Neurodegeneration in the 5xFAD Mouse Model of Alzheimer's Disease: Role of CCL2
dc.typejournal article
dc.type.hasVersionVoR
dc.volume.number56
dspace.entity.typePublication
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