Huntington’s disease (HD) is a genetic neurodegenerative disease caused by a polyglutamine expansion in the protein huntingtin. The age of symptom onset has been correlated with the length of this repeat. Adults with a repeat length of greater than 35 polyglutamines typically present symptoms between the ages of 40 and 50. Greater than 60 polyglutamine repeats causes a rapidly progressing early onset of the disease in adolescents. While both types of HD result in cognitive deficits and neuron loss, 25-35% of early-onset HD patients exhibit epileptic seizures that become less responsive to anti-epileptics over time. One of the earliest molecular changes in HD is the loss of the cannabinoid receptor 1 (CB1) before symptom onset. Activation of CB1 inhibits the release of neurotransmitters and protects neurons from cell death, whereas genetic deletion in HD models exacerbates motor symptoms. Additionally, activation of CB1 prevents the onset of seizures. The goal of this study was to determine if loss of CB1 activation increased epileptic activity, decreased survival, and whether elevating endocannabinoid (CB1 agonists) levels reversed these effects in early-onset HD. R6/2 mice (a rapidly progressing mouse model of early-onset HD) were treated with SR141716A (a CB1 antagonist), WWL123 (elevates the level of endocannabinoids), or vehicle (a control) and the frequency and severity of spontaneous and handling-induced seizures were analyzed. Preliminary results demonstrated that R6/2 mice treated with SR141716A had a decreased lifespan and more frequent seizures whereas WWL123 decreased seizure severity. This suggests that the endocannabinoid system has a regulatory effect on seizures associated with early-onset HD. Future experiments in the lab will further characterize the role of endocannabinoids and CB1 in early-onset HD seizures as a novel therapeutic pathway.

Rhododendron is an aesthetically valuable plant genus primarily distributed in Northern hemisphere. Previous work by collectors and taxonomists has revealed that Rhododendron taxa have a scattered pattern of distribution around the globe. Yet, the evolutionary history that led to this modern distribution pattern is not well understood. Fossil records of once extant Rhododendron populations can be a key component for inferring the diversification and migration of Rhododendron. Macrofossils such as leaves and stems have more restricted requirements in their formation, and hence are rarely discovered. On the contrary, microfossils of pollen are more widely preserved and found. In this study, I explored the potential of using pollen microfossils of Rhododendron to understand how the modern distribution pattern of Rhododendrons came about. To that end, I compared and contrasted modern Rhododendron pollen from three subgenera and twenty four subsections in order to discover the degree of consistency in pollen morphology within and unique combination of traits of each taxon. All observations were performed under light microscopy. Experimental data include both structural differences and quantitative measurements. Preliminary results demonstrate promising level of variation in measurements such as the structure of apperture edges, pollen wall sculpture, overall size, and wall thickness. These palynological features are then fitted into a Rhododendron phylogeny based on molecular data to reveal any potential taxonomic significance of variation in pollen morphology. 

Huntington’s disease is a hereditary neurodegenerative disease that is characterized by motor and cognitive dysfunction and currently has no known cure. One of the earliest molecular events in Huntington’s disease pathogenesis is the down-regulation of the cannabinoid 1 receptor (CB₁), occurring prior to symptom onset and loss of any other receptor. Though the exact mechanism is unclear, it has been shown that CB₁ loss occurs almost exclusively in medium spiny neurons (MSNs), cells that play a key role in movement and degenerate later in disease progression. CB₁ knockouts in mouse models also exhibit exacerbated disease phenotype. Previous studies have attempted to rescue CB₁ function in mouse models by administering chronic cannabinoid agonists, but have produced inconclusive results. Our study investigates the effects of CB₁ receptor rescue from a genetic approach, by inserting flox-stop CB₁ (fsCB₁) specifically activated in striatal MSNs of R6/2 mice, the best characterized Huntington’s disease mouse model. We first confirmed the localization and functionality of the knocked-in fsCB₁ in R6/2 and CB₁ null mice (control), and then measured motor phenotype and synaptic integrity over time. Performance of R6/2 mice with and without fsCB₁ rescue was measured using rotarod, open field, novel object recognition, and clasping behavior tests biweekly from weeks 4 to 12 of age. MSN axon integrity was measured by IHC staining for caspase-6 and NPY-Y1R, markers for Wallerian-type degeneration. By observing behavior and axon integrity from pre- through late-symptomatic stages, we hope to establish a relationship between early MSN axonal loss and impaired motor phenotype in R6/2 mice, as well as link CB₁ function to axonal integrity through R6/2 and fsCB₁-R6/2 comparisons. This research will increase the present understanding of molecular mechanisms behind Huntington’s disease and provide insight into CB₁ as a therapeutic target.