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PeerJ. 2017 Oct 31;5:e3905. doi: 10.7717/peerj.3905. eCollection 2017.

A novel animal model for neuroinflammation and white matter degeneration.

Author information

1
Department of Psychiatry, University of California, San Diego, La Jolla, CA, United States of America.
2
Department of Anesthesiology, University of California, San Diego, La Jolla, CA, United States of America.
3
Research Service, VA San Diego Healthcare System, San Diego, CA, USA.

Abstract

Small interference RNA has been widely used to suppress gene expression. Three different short hairpin RNAs (shRNAs) against dopamine D1 receptor (Drd1), driven by mouse U6 promoter in self-complementary AAV8 vector (scAAV8), were used to silence mouse striatal Drd1 expression. Transduction of mouse striatum with all three scAAV8-D1shRNA viruses, but not the control scAAV8 virus, causes extensive neuroinflammation, demyelination, and axon degeneration. RNA interference is known to be coupled to the innate immune system as a host cell defense against virus infection. Activation of the innate immune system may play a causal role in the development of neuroinflammation and white matter degeneration, providing a novel animal model for multiple sclerosis (MS) and other neuroinflammatory diseases.

KEYWORDS:

Drd1; Innate immunity; Microglial activation; Neuroinflammation; White matter degeneration; shRNA

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