RT Journal Article
T1 Should We Open Fire on Microglia? Depletion Models as Tools to Elucidate Microglial Role in Health and Alzheimer's Disease.
A1 Romero-Molina, Carmen
A1 Navarro, Victoria
A1 Jimenez, Sebastian
A1 Muñoz-Castro, Clara
A1 Sanchez-Mico, Maria V
A1 Gutierrez, Antonia
A1 Vitorica, Javier
A1 Vizuete, Marisa
K1 Alzheimer’s disease
K1 depletion
K1 inflammation
K1 microglia
AB 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 We also reported unpublished data from our genetic microglial depletion model, Cx3cr1CreER/Csf1rflx/flx, in which we temporally controlled microglia depletion by either intraperitoneal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.
YR 2021
FD 2021-09-08
LK https://hdl.handle.net/10668/26317
UL https://hdl.handle.net/10668/26317
LA en
DS RISalud
RD Apr 12, 2025