Effects of inhibiting mTOR with rapamycin on behavior, development, neuromuscular physiology, and cardiac function in larval Drosophila

Abstract

Rapamycin and other mTOR inhibitors are being heralded as possible treatments for many human ailments. It is currently being utilized clinically as an immunomodulator after transplantation procedures and treatment for certain forms of cancer, but it has numerous potential clinical indications. Some studies have shown profound effects on life cycle and muscle physiology, but these issues have not been addressed in an organism undergoing developmental processes. This paper fills this void by examining the effect of mTOR inhibition by rapamycin on several different qualities of larval Drosophila. Various dosages of the compound were fed to second instar larvae. These larvae were monitored for pupae formation to elucidate possible life cycle effects, and a delay to pupation was quantified. Behavioral deficits were documented in rapamycin treated larvae. Electrophysiological measurements were taken to discern changes in muscle physiology and synaptic signaling (i.e., resting membrane potential, amplitude of excitatory post-synaptic potentials, synaptic facilitation). Pupation delay and effects on behavior which are likely due to synaptic alterations within the CNS were discovered in rapamycin-fed larvae. These results allow for several conclusions as to how mTOR inhibition by rapamycin affects a developing organism. This could eventually allow for a more informed decision when using rapamycin and other mTOR inhibitors to treat human diseases, especially in children and adolescents to account for known side effects.