Discipline: Biological Sciences
Subcategory: Physiology and Health
Andrew Blake - Delaware State University
Co-Author(s): Arianna Wallace and Hakeem Lawal, Delaware State University, Dover, DE
Decline in cholinergic neurotransmission is associated with normal and pathological aging. Cholinergic therefore release remains a subject of great interest to human biology. However, the precise role of changes in acetylcholine release in mediating behaviors, such as locomotion, remain poorly understood. The vesicular acetylcholine transporter (VAChT) is present in many species, including worms, flies, and humans, and is responsible for the packaging and transport of acetylcholine for exocytotic release. A complete loss of VAChT function is lethal, while severe mutations can cause decreased locomotive performance in Drosophila. Here, we hypothesize that deficits in Vacht function can be rescued by a pharmacological or genetic increase in VAChT, which can be identifiable by a shift in the rate of locomotion towards normal.
The overall purpose of this study was to determine an effective method of rescuing mutations in Drosophila Vacht. In order to rescue the locomotion deficit seen in Vacht mutants, cholinergic drugs in different concentrations were administered to the Vacht mutant larvae for two hour time period; dimethyl sulfoxide or water were used a vehicle (and therefore was a control). Drug or vehicle only fed larvae were then tested in two locomotion assays, using the automated MultiWorm Tracker, and the touch response assay. We report that treatment with brucine (an acetylcholine agonist) rescues the locomotion defect in three Vacht mutant alleles. The results indicate that genetic deficits in the vesicular acetylcholine transporter can be repaired using pharmacological methods. Our future directions include determining the full spectrum of cholinergic drugs that are able to rescue this phenotype and determining the mechanism through which these chemical alter cholinergic signaling. Together, these studies could pave way for future methods used to treat human disorders, such as Alzheimer’s disease, that are associated with defective cholinergic signaling.
Funder Acknowledgement(s): NSF HBCU-UP HRD-1533631
Faculty Advisor: Hakeem Lawal,