Evaluation of caffeine and taurine administration in improving neurodegenerative dysfunction in Caenorhabditis elegans overexpressing the APP ortholog: APL-1

Moultrie, GA

INTRODUCTION: Alzheimer’s Disease (AD) is characterized by an over-accumulation of β-amyloid plaques and neurofibrillary Tau tangles present within the brain, contributing to associative neurodegeneration. Taurine is an essential amino acid found within the nervous system; however, it is one of a few amino acids not required in routine protein synthesis. Caffeine and taurine have both been identified as active ingredients in energy drinks with the benefit of improving nervous system function, supporting neural recovery, and synaptogenesis. In previous studies, taurine has been shown to increase memory retention in animal models, and consumption of caffeine reflects improvement in locomotion, memory, and lifespan.

OBJECTIVES: This project aims to determine the impact of caffeine and taurine on a mutant C. elegans strain, ynIs-79, which over-expresses the amyloid precursor protein ortholog, APL-1 within its nervous system. We expect that supplementing the mutant ynIs-79 nematode’s diet with caffeine and/or taurine will positively influence the observed neurodegenerative dysfunction by reducing the number of taps required to induce habituation. We hypothesize that treating the nematodes with caffeine and/or taurine will result in a statistically significant decrease in the number of taps required to induce a habitual response and for the mutant nematodes to associate it as a non-harmful stimulus. This would suggest an improvement in memory and neurodegenerative dysfunction.

METHODS: This was an observational study assessing the effects of caffeine and taurine administration and improvements in neurodegenerative dysfunction in a dose-dependent manner. The primary endpoint was the number of taps required to induce habituation and theoretically improve learning and movement in C. elegans. For comparison, we assessed anterior and posterior habituation following exposure to caffeine or taurine by tapping the worms with a sterile eyelash until the nematodes recognized the taps as a non-threatening stimulus. Control and mutant C. elegans were treated with 250μL of caffeine or taurine separately, at the following drug concentrations: 0μg/mL(control), 1μg/mL, 10μg/mL, 250μg/mL, and 500μg/mL.

RESULTS: Thirty nematodes were tapped on the anterior and posterior ends after application of caffeine and/or taurine at varying concentrations. Current preliminary results indicate a significant decrease in the number of taps required for habituation in the mutant ynIs-79 C. elegans strain, comparatively. Statistical analysis included a one-way ANOVA and Dunnett’s multiple comparison test for repeated measures using Prism.

CONCLUSION: The administration of caffeine towards mutant ynIs-79 C. elegans leads to improvements in observed neurodegenerative dysfunction at higher concentrations of caffeine by reducing the threshold required to induce habituation. However, administration of taurine does not reflect a dose-dependent reduction in the number of taps required to elicit habituation. Rather, administration of taurine at minimal concentrations is sufficient to achieve the desired effect. Repeated studies are needed to provide for targeted assessment of anterior and posterior response to tap habituation separately. Testing the same worm for both anterior and posterior response may provide for overstimulation of the nematode and reflect increased variability in the data.