RT Journal Article
T1 Reboxetine Treatment Reduces Neuroinflammation and Neurodegeneration in the 5xFAD Mouse Model of Alzheimer's Disease: Role of CCL2
A1 López Gutiérrez, Irene
A1 García Bueno, Borja
A1 Caso Fernández, Javier Rubén
A1 García Bueno, Borja
A1 Leza Cerro, Juan Carlos
A1 Muñoz Madrigal, José Luis
AB The 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.
PB Springer
SN 0893-7648
YR 2019
FD 2019-07-11
LK https://hdl.handle.net/20.500.14352/88880
UL https://hdl.handle.net/20.500.14352/88880
LA eng
NO Universidad Complutense de Madrid
NO Spanish Ministry of Science
NO Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM)
NO European Youth Employment Initiative (YEI)
DS Docta Complutense
RD 28 sept 2024