Artículo
Should we open fire on microglia? Depletion models as tools to elucidate microglial role in health and alzheimer’s disease
Autor/es | Romero Molina, Carmen
Navarro Garrido, Victoria Jiménez Muñoz, Sebastián Muñoz Castro, Clara Sánchez Mico, María Gutiérrez, Antonia Vitorica Ferrández, Francisco Javier Vizuete Chacón, María Luisa |
Departamento | Universidad de Sevilla. Departamento de Bioquímica y Biología Molecular |
Fecha de publicación | 2021 |
Fecha de depósito | 2021-09-20 |
Publicado en |
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Resumen | Microglia play a critical role in both homeostasis and disease, displaying a wide variety in terms of density, functional markers and transcriptomic profiles along the different brain regions as well as under injury or ... Microglia play a critical role in both homeostasis and disease, displaying a wide variety in terms of density, functional markers and transcriptomic profiles along the different brain regions as well as under injury or pathological conditions, such as Alzheimer’s disease (AD). The generation of reliable models to study into a dysfunctional microglia context could provide new knowledge towards the contribution of these cells in AD. In this work, we included an overview of different microglial depletion approaches. We also reported unpublished data from our genetic microglial depletion model, Cx3cr1CreER /Csf1rflx/flx, in which we temporally controlled microglia depletion by either intraperitoneal (acute model) or oral (chronic model) tamoxifen administration. Our results reported a clear microglial repopulation, then pointing out that our model would mimic a context of microglial replacement instead of microglial dysfunction. Next, we evaluated the origin and pattern of microglial repopulation. Additionally, we also reviewed previous works assessing the effects of microglial depletion in the progression of Aβ and Tau pathologies, where controversial data are found, probably due to the heterogeneous and time-varying microglial phenotypes observed in AD. Despite that, microglial depletion represents a promising tool to assess microglial role in AD and design therapeutic strategies. |
Agencias financiadoras | Instituto de Salud Carlos III PI18/01556, PI18/01557 |
Identificador del proyecto | PI18/01556
PI18/01557 20141432 20141431 CB06/05/0094 CB06/05/1116 US-1262734 UMA18-FEDERJA-211 P18-RT-2233 |
Cita | Romero Molina, C., Navarro Garrido, V., Jiménez Muñoz, S., Muñoz Castro, C., Sánchez Mico, M., Gutiérrez, A.,...,Vizuete Chacón, M.L. (2021). Should we open fire on microglia? Depletion models as tools to elucidate microglial role in health and alzheimer’s disease. International Journal of Molecular Sciences, 22 (18), 9734. |
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