Frontiers in immunology · 2026
Microglial dectin-1/Clec7a in an alzheimer's disease model: a double-edged sword across the lifespan.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Xi Wen, Rodriguiz Ramona M, Wetsel William C, Shinohara Mari L
Аннотация
INTRODUCTION: Dectin-1, encoded by Clec7a, is highly expressed in disease-associated microglia in Alzheimer's disease (AD), yet its in vivo function remains largely unknown.
METHODS: We generated Clec7a-floxed mice and conditionally deleted dectin-1 in microglia to determine its effects on pathology and behavior using the 5xFAD mice model. No dectin-1 ligand injection was used. Amyloid pathology, immune phenotypes in the brain, and behavior were examined across disease stages.
RESULTS: In 6-month (mo) old mice, microglial dectin-1 reduced dense Aβ plaques in the subiculum without detectable behavioral effects. At 9-mo, microglial dectin-1 impaired memory retention and spatial learning, accompanied by an increased diffuse/dense Aβ plaque ratio in the hilus of the dentate gyrus and limited brain infiltration of Ly6Glo neutrophils. At 16-mo, microglial dectin-1 increased freezing behavior suggestive of heightened emotional reactivity.
DISCUSSION: Microglial dectin-1 exerts age-dependent effects: beneficial for amyloid pathology in mid-life but detrimental for cognition and anxiety-related behavior in later life. These context-specific outcomes highlight the need to consider age, the cell types expressing dectin-1, and dectin-1-activating ligands. Future studies should define the classes of ligands and signaling landscape of microglial dectin-1 across the disease course with the goal of identifying windows where intervention could tilt its function toward sustained neuroprotection.
METHODS: We generated Clec7a-floxed mice and conditionally deleted dectin-1 in microglia to determine its effects on pathology and behavior using the 5xFAD mice model. No dectin-1 ligand injection was used. Amyloid pathology, immune phenotypes in the brain, and behavior were examined across disease stages.
RESULTS: In 6-month (mo) old mice, microglial dectin-1 reduced dense Aβ plaques in the subiculum without detectable behavioral effects. At 9-mo, microglial dectin-1 impaired memory retention and spatial learning, accompanied by an increased diffuse/dense Aβ plaque ratio in the hilus of the dentate gyrus and limited brain infiltration of Ly6Glo neutrophils. At 16-mo, microglial dectin-1 increased freezing behavior suggestive of heightened emotional reactivity.
DISCUSSION: Microglial dectin-1 exerts age-dependent effects: beneficial for amyloid pathology in mid-life but detrimental for cognition and anxiety-related behavior in later life. These context-specific outcomes highlight the need to consider age, the cell types expressing dectin-1, and dectin-1-activating ligands. Future studies should define the classes of ligands and signaling landscape of microglial dectin-1 across the disease course with the goal of identifying windows where intervention could tilt its function toward sustained neuroprotection.