Safety of Striatal Infusion of siRNA in a Transgenic Huntington's Disease Mouse Model.

ABSTRACT:

Background

The immune system In Huntington's disease (HD) is activated and may overreact to some therapies. RNA interference using siRNA lowers mutant huntingtin (mHTT) protein but could increase immune responses.

Objective

To examine the innate immune response following siRNA infusion into the striatum of wild-type (WT) and HD transgenic (YAC128) mice.

Methods

siRNAs (2'-O-methyl phosphorothioated) were infused unilaterally into striatum of four month-old WT and YAC128 mice for 28 days. Microglia number and morphology (resting (normal), activated, dystrophic), cytokine levels, and DARPP32-positive neurons were measured in striatum immediately or 14 days post-infusion. Controls included contralateral untreated striatum, and PBS and sham treated striata.

Results

SUBMITTER: Johnson E 

PROVIDER: S-EPMC5058343 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature