Weeding Out the Truth: Can We Reduce Neuroinflammation in Huntington's Disease?

Huntington's disease (HD) is an autosomal-dominant, neurodegenerative disorder characterized by unwanted choreatic movements, cognitive decline, and behavioral and psychiatric difficulties. The mutant protein that causes HD results from an abnormal expansion of the CAG repeat segment on the HTT gene. This protein becomes prone to aggregation, resulting in neuron dysfunction and degeneration. The striatum is crucial for regulating voluntary movement and is the primary region affected. While neurons are found in abundance, glial cells-namely microglia and astrocytes-are the most abundant cell type in the striatum. When in a resting state, these cells work to clear debris and modulate neuronal signaling. However, when these cells become activated-which is a form of reactive gliosis-in response to the mutant HTT protein, neuroinflammation occurs and synaptic connections between neurons are lost. The immediate cause of HD is well known, but the molecular mechanism of reactive gliosis driving neuroinflammation in the striatum remains understudied and unclear. Furthermore, there is no current cure for this extremely progressive, fatal disease. This research study aimed to fill these gaps in the literature by gaining a better understanding of the use of cannabidiol (CBD) as a possible therapeutic for neuroinflammation in Q140 mouse models of HD. CBD has been shown to improve chorea in Parkinson's disease and reduce seizures in epilepsy, but thus far little is known about the possible effects on HD. Mice were given CBD treatment or MCT oil vehicle control for three months. Behavioral assays including rotarod, open field, ladder crossing, and light and dark box were used to assess motor performance. The brains were then extracted and tissue was stained with fluorescent proteins and imaged with a confocal microscope. Numerous methods and techniques such as genotyping, behavioral tests, perfusions, immunohistochemistry, and tissue imaging were utilized to reach the final glial cell quantification. Contrary to our hypothesis, this preclinical trial did not yield the expected outcome but rather produced unexpected yet positive results. The final results are proprietary and withheld from this abstract until published in a scientific journal, but we believe that they show promise for future preclinical trials to determine the full therapeutic effects of CBD on glial cell morphologies in HD. [This abstract is a placeholder. The project will be linked to this page after it is published elsewhere.]