Investigating the Effects of Neurotransmitter Supplementation on C. Elegans That Carries the Human Homolog of the Mutant Huntingtin Gene

Abstract

Significance of Topic: Huntington’s Disease is a chronic, incurable, and deadly disease caused by the inheritance of a dominant gene, wreaking havoc within families generation by generation.

Theoretical Considerations: The nematode (worm) C. Elegans is a powerful model for studying human diseases because they share a relatively recent common ancestor with humans, and many of the same human disease-causing genes are conserved. The mutant Huntingtin gene contains an excess of glutamine (CAG) repeats, and this causes the protein to stick to itself. These accumulate into larger aggregates that disrupt healthy neurotransmitter synthesis (within cells) and synaptic release (communication between cells). This results in the degeneration of neurons that control movement, such as those within the Basal Ganglia (in humans), causing involuntary muscle movement.

Research Question: Can the administration of exogenous neurotransmitters normalize motor behavior in C. Elegans with the mutant Huntingtin gene?

Methodology: First, we will administer solutions of dopamine, serotonin, acetylcholine, and GABA at varying concentrations and combinations to C. Elegans with the mutant Huntingtin Gene. Then, record the frequency of thrashing and C-shaped turns of mutant C. Elegans (a) exposed to neurotransmitters, (b) mutants unexposed, and (c) wild type exposed to neurotransmitters while looking for an effect on motor behavior. During this process, we will record additional observations on the muscle contraction frequencies of the pharynx, sphincter, vulva, and measurement of the number of eggs released.

Expected Findings: We predict at high concentrations of solutions of single neurotransmitters, the mutant C. Elegans will be immobilized, and at lower concentrations, they will have slowed movement. We expect that with equal amounts of low-concentration stimulatory and inhibitory neurotransmitters, the mutant C. Elegans will exhibit normalized motor behavior.

Details

Session 1

9:30am – 11:00am

Grand Salon