Microglia, HIV and drugs of abuse

我们正在研究啮齿动物的小胶质细胞如何在慢性和急性暴露模型中对精神兴奋剂如甲基苯丙胺作出反应。正在进行的工作已经确定了甲基苯丙胺的剂量，可以引起纹状体中小胶质细胞的独特激活，这可以用来研究激活的小胶质细胞如何影响周围的神经元。

We are examining how rodent microglia respond to psychostimulants such as methamphetamine in both a chronic and acute exposure model. Ongoing work has identified dosing of methamphetamine that causes unique activation of microglia in the striatum that can be used to examine how activated microglia can affect the surround neurons. We have recently developed a novel microglial cell line that has a modified HIV provirus inserted into the genome. This provirus lacks the gag and pol genes but expresses a luciferase which can be used to monitor effectors of proviral transcriptional activity. We have used CRISPR to target the long terminal repeat (LTR) promoter of HIV in this cell line and are using it to evaluate CRISPR-based approaches to alter HIV proviral activity in microglia. Microglia are notoriously difficult to target with transgenic material. We have recently identified an AAV vector capable of expressing in rat microglia. We are also working on a non-viral approach to delivery transgenic material (DNA, RNA, CRISPR ribonucleoproteins) to microglia. These tools will allow us to more readily examine the effect of microglia production of HIV proteins and the effects on surrounds in neurons when exposed to substances of addiciton.