Should we open fire on microglia? Depletion models as tools to elucidate microglial role in health and alzheimer’s disease
|Author||Romero Molina, Carmen
Navarro Garrido, Victoria
Muñoz Castro, Clara
Sánchez Mico, María
Vitorica Ferrández, Francisco Javier
Vizuete Chacón, María Luisa
|Department||Universidad de Sevilla. Departamento de Bioquímica y Biología Molecular|
|Abstract||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 We also reported unpublished data from our genetic microglial depletion model, Cx3cr1CreER /Csf1rflx/flx, in which we temporally controlled microglia depletion by either intraperitoneal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.
|Funding agencies||Instituto de Salud Carlos III PI18/01556, PI18/01557|
|Citation||Romero Molina, C., Navarro Garrido, V., Jiménez, S., Muñoz Castro, ., 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.|