Microglial microRNAs mediate sex-specific responses to tau pathology

Lay Kodama; Elmer Guzman; Jon I Etchegaray; Yaqiao Li; Faten A Sayed; Lu Zhou; Yungui Zhou; Lihong Zhan; David Le; Joe C Udeochu; Claire D Clelland; Zuolin Cheng; Guoqiang Yu; Qingyun Li; Kenneth S Kosik; Li Gan

doi:10.1038/s41593-019-0560-7

Microglial microRNAs mediate sex-specific responses to tau pathology

Nat Neurosci. 2020 Feb;23(2):167-171. doi: 10.1038/s41593-019-0560-7. Epub 2019 Dec 23.

Authors

Lay Kodama^{1

2

3

4}, Elmer Guzman^{5

6}, Jon I Etchegaray², Yaqiao Li², Faten A Sayed^{1

2}, Lu Zhou⁷, Yungui Zhou², Lihong Zhan², David Le², Joe C Udeochu³, Claire D Clelland^{2

8}, Zuolin Cheng⁹, Guoqiang Yu⁹, Qingyun Li⁷, Kenneth S Kosik^{5

6}, Li Gan^{10

11

12}

Affiliations

¹ Neuroscience Graduate Program, University of California, San Francisco, San Francisco, CA, USA.
² Gladstone Institute of Neurological Disease, San Francisco, CA, USA.
³ Helen and Robert Appel Alzheimer's Disease Research Institute, Brain and Mind Research Institute, Weill Cornell Medicine, NY, New York, USA.
⁴ Medical Scientist Training Program and Neuroscience Graduate Program, University of California, San Francisco, San Francisco, CA, USA.
⁵ Department of Molecular, Cell and Developmental Biology, University of California, Santa Barbara, Santa Barbara, CA, USA.
⁶ Neuroscience Research Institute, University of California, Santa Barbara, Santa Barbara, CA, USA.
⁷ Department of Neurobiology, Stanford University School of Medicine, Stanford, CA, USA.
⁸ Department of Neurobiology, University of California, San Francisco, San Francisco, CA, USA.
⁹ Bradley Department of Electrical and Computer Engineering, Virginia Polytechnic Institute and State University, Arlington, VA, USA.
¹⁰ Neuroscience Graduate Program, University of California, San Francisco, San Francisco, CA, USA. [email protected].
¹¹ Gladstone Institute of Neurological Disease, San Francisco, CA, USA. [email protected].
¹² Helen and Robert Appel Alzheimer's Disease Research Institute, Brain and Mind Research Institute, Weill Cornell Medicine, NY, New York, USA. [email protected].

Abstract

Sex is a key modifier of neurological disease outcomes. Microglia are implicated in neurological diseases and modulated by microRNAs, but it is unknown whether microglial microRNAs have sex-specific influences on disease. We show in mice that microglial microRNA expression differs in males and females and that loss of microRNAs leads to sex-specific changes in the microglial transcriptome and tau pathology. These findings suggest that microglial microRNAs influence tau pathogenesis in a sex-specific manner.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Brain / metabolism
Brain / pathology*
Female
Male
Mice
MicroRNAs / metabolism*
Microglia / metabolism*
Microglia / pathology
Sex Characteristics*
Tauopathies / metabolism
Tauopathies / pathology*
Transcriptome
tau Proteins / metabolism

Substances

MicroRNAs
tau Proteins

Abstract

Publication types

MeSH terms

Substances

Grants and funding