Increased Microglial Activity, Impaired Adult Hippocampal Neurogenesis, and Depressive-like Behavior in Microglial VPS35-Depleted Mice

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Joanna R ErionWen-Cheng Xiong

Abstract

Vacuolar sorting protein 35 (VPS35) is a critical component of retromer, which is essential for selective endosome-to-Golgi retrieval of membrane proteins. VPS35 deficiency is implicated in neurodegenerative disease pathology, including Alzheimer's disease (AD). However, exactly how VPS35 loss promotes AD pathogenesis remains largely unclear. VPS35 is expressed in various types of cells in the brain, including neurons and microglia. Whereas neuronal VPS35 plays a critical role in preventing neurodegeneration, the role of microglial VPS35 is largely unknown. Here we provide evidence for microglial VPS35's function in preventing microglial activation and promoting adult hippocampal neurogenesis. VPS35 is expressed in microglia in various regions of the mouse brain, with a unique distribution pattern in a brain region-dependent manner. Conditional knocking out of VPS35 in microglia of male mice results in regionally increased microglial density and activity in the subgranular zone of the hippocampal dentate gyrus (DG), accompanied by elevated neural progenitor proliferation, but decreased neuronal differentiation. Additionally, newborn neurons in the mutant DG show impaired dendritic morphology and reduced dendritic spine density....Continue Reading

Citations

Sep 14, 2020·The European Journal of Neuroscience·Tasuku ArakiRyuta Koyama
Nov 22, 2018·Frontiers in Cellular Neuroscience·Lijuan ZhangZili You
Nov 9, 2018·Frontiers in Synaptic Neuroscience·Lennart Brodin, Oleg Shupliakov
Mar 21, 2019·Frontiers in Cell and Developmental Biology·Noelia Rodríguez-IglesiasJorge Valero
Sep 24, 2020·International Journal of Molecular Sciences·Mohammed Al-OnaiziAyman ElAli
Jun 6, 2019·Cell and Tissue Research·Seon-Cheol Park
Nov 3, 2020·Frontiers in Neuroscience·Ricardo Jesus Martinez-TapiaLuz Navarro
Dec 4, 2020·Science Translational Medicine·Scott A Small, Gregory A Petsko
Feb 27, 2021·Stem Cell Reports·Kelsey R BabcockAshley E Webb
Jul 6, 2021·Frontiers in Neuroscience·Arthur Sefiani, Cédric G Geoffroy
Aug 1, 2021·Nature Communications·Hanxiao LiuQiaojie Xiong
Nov 7, 2021·Cell & Bioscience·Lei XiongWen-Cheng Xiong

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