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Open Access 01-12-2019 | Stroke | Research

Microglial VPS35 deficiency regulates microglial polarization and decreases ischemic stroke-induced damage in the cortex

Authors: Shi-Yang Ye, Joanna E. Apple, Xiao Ren, Fu-Lei Tang, Ling-Ling Yao, Yong-Gang Wang, Lin Mei, Yuan-Guo Zhou, Wen-Cheng Xiong

Published in: Journal of Neuroinflammation | Issue 1/2019

Abstract

Background

Vacuolar sorting protein 35 (VPS35), a critical component of retromer, is essential for selective endosome-to-Golgi retrieval of membrane proteins. It is highly expressed in microglial cells, in addition to neurons. We have previously demonstrated microglial VPS35’s functions in preventing hippocampal, but not cortical, microglial activation, and in promoting adult hippocampal neurogenesis. However, microglial VPS35’s role in the cortex in response to ischemic stroke remains largely unclear.

Methods

We used mice with VPS35 cKO (conditional knockout) in microglial cells and examined and compared their responses to ischemic stroke with control mice. The brain damage, cell death, changes in glial cells and gene expression, and sensorimotor deficits were assessed by a combination of immunohistochemical and immunofluorescence staining, RT-PCR, Western blot, and neurological functional behavior tests.

Results

We found that microglial VPS35 loss results in an increase of anti-inflammatory microglia in mouse cortex after ischemic stroke. The ischemic stroke-induced brain injury phenotypes, including brain damage, neuronal death, and sensorimotor deficits, were all attenuated by microglial VPS35-deficiency. Further analysis of protein expression changes revealed a reduction in CX3CR1 (CX3C chemokine receptor 1) in microglial VPS35-deficient cortex after ischemic stroke, implicating CX3CR1 as a potential cargo of VPS35 in this event.

Conclusion

Together, these results reveal an unrecognized function of microglial VPS35 in enhancing ischemic brain injury-induced inflammatory microglia, but suppressing the injury-induced anti-inflammatory microglia. Consequently, microglial VPS35 cKO mice exhibit attenuation of ischemic brain injury response.

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Title: Microglial VPS35 deficiency regulates microglial polarization and decreases ischemic stroke-induced damage in the cortex
Authors: Shi-Yang Ye
Joanna E. Apple
Xiao Ren
Fu-Lei Tang
Ling-Ling Yao
Yong-Gang Wang
Lin Mei
Yuan-Guo Zhou
Wen-Cheng Xiong
Publication date: 01-12-2019
Publisher: BioMed Central
Keyword: Stroke
Published in: Journal of Neuroinflammation / Issue 1/2019
Electronic ISSN: 1742-2094
DOI: https://doi.org/10.1186/s12974-019-1633-y

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Microglial VPS35 deficiency regulates microglial polarization and decreases ischemic stroke-induced damage in the cortex

Abstract

Background

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

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