RT Journal Article
T1 Inflammatory Response in the Hippocampus of PS1M146L/APP751SL Mouse Model of Alzheimer’s Disease: Age-Dependent Switch in the Microglial Phenotype from Alternative to Classic.
A1 Jiménez, Sebastián
A1 Baglietto-Vargas, David
A1 Caballero, Cristina
A1 Moreno-González, Inés
A1 Torres, Manuel
A1 Sánchez-Varo, Raquel María
A1 Ruano, Diego
A1 Vizuete, Marisa
A1 Gutiérrez-Pérez, Antonia
A1 Vitorica Ferrández, Javier
K1 Alzheimer, Enfermedad de - Modelos animales
K1 Microglia
K1 Hipocampo (Cerebro)
AB Although the microglial activation is concomitant to the Alzheimer's disease, its precise role (neuroprotection vs neurodegeneration) has not yet been resolved. Here, we show the existence of an age-dependent phenotypic change of microglial activation in the hippocampus of PS1xAPP model, from an alternative activation state with Aβ phagocytic capabilities (at 6 months) to a classic cytotoxic phenotype (expressing TNF-α and related factors) at 18 months of age. This switch was coincident with high levels of soluble Aβ oligomers and a significant pyramidal neurodegeneration. In vitro assays, using astromicroglial cultures, demonstrated that oligomeric Aβ42 and soluble extracts from 18-month-old PS1xAPP hippocampus produced a potent TNF-α induction whereas monomeric Aβ42 and soluble extract from 6- or 18-month-old control and 6-month-old PS1xAPP hippocampi produced no stimulation. This stimulatory effect was avoided by immunodepletion using 6E10 or A11. In conclusion, our results show evidence of a switch in the activated microglia phenotype from alternative, at the beginning of Aβ pathology, to a classical at advanced stage of the disease in this model. This change was induced, at least in part, by the age-dependent accumulation of extracellular soluble Aβ oligomers. Finally, these cytotoxic activated microglial cells could participate in the neuronal lost observed in AD.
PB Society for Neuroscience
YR 2008
FD 2008
LK https://hdl.handle.net/10630/31853
UL https://hdl.handle.net/10630/31853
LA eng
NO Jimenez S, Baglietto-Vargas D, Caballero C, Moreno-Gonzalez I, Torres M, Sanchez-Varo R, Ruano D, Vizuete M, Gutierrez A, Vitorica J. Inflammatory response in the hippocampus of PS1M146L/APP751SL mouse model of Alzheimer's disease: age-dependent switch in the microglial phenotype from alternative to classic. J Neurosci. 2008 Nov 5;28(45):11650-61. doi: 10.1523/JNEUROSCI.3024-08.2008. PMID: 18987201; PMCID: PMC6671312.
NO Política de acceso abierto tomada de: https://v2.sherpa.ac.uk/id/publication/14136?template=romeo
NO Fondo de Investigación Sanitaria (FIS) del Instituto de Salud Carlos III de España, ref. PI060567 (J.V.), PI060556 (A.G.), y PI060781 (D.R.).Junta de Andalucía, Proyecto de Excelencia CVI-902. S.J. y I.M.-G. contratados CIBERNED. D.B.-V. y M.T. becas de la Junta de AndalucíaR.S.-V. y C.C. becas del Ministerio de Educación y Ciencia (MEC) de España.
DS RIUMA. Repositorio Institucional de la Universidad de Málaga
RD 21 ene 2026