SEROTONIN-MEDIATED MITOCHONDRIAL BIOGENESIS AND ITS IMPLICATIONS IN DROSOPHILA SURVIVAL & BEHAVIOR

Abstract

Serotonin is a neurotransmitter that plays a role in several psychological and physiological processes. Studies have shown that serotonin decreases apoptosis and increases healing and cell survival significantly in human cells. However, how serotonin regulates these processes remains largely unknown. Mitochondria in neurons have a significant role in bioenergetics, the control of synaptic signal transmission, and stress tolerance. Moreover, mitochondria dysfunction has been linked to inherited and acquired neurological disorders like Alzheimer's and Parkinson’s, Recent studies have shown that elevated serotonin and 5-hydroxytryptamine receptor 1F (5-HT1F) activation can promote mitochondrial biogenesis in dopaminergic neurons in rodents. However, these studies lack information on the effect of serotonin on mitochondrial biogenesis in all neurons and its effects on survival and behavior. In our study, we hypothesize that serotonin may regulate mitochondrial biogenesis globally and affect Drosophila melanogaster cell viability, survival rate, and social interaction. To test this, we used pharmacological and genetic strategies to enhance serotonin levels in Drosophila to determine the effect of serotonin on the mitochondria morphology and function and to check its underlying molecular pathway. According to our observations, elevated levels of serotonin had effects on mitochondrial biogenesis with changes in number, area, circularity, and length of mitochondria in different brain regions. Moreover, serotonin played a role in oxidative stress adaptation, maintaining mitochondrial membrane potential, enhancing survival rate, and affecting behavior like increasing social interaction. However, our results show that serotonin did not cause significant change in the expression of the major mitochondrial dynamic genes. Together, our results show the crucial role of serotonin in regulation of mitochondrial biogenesis and function and thus enabling the organism to adapt to stress and promoting its survival rate and modulate its social interaction behaviors.

Date of Award	2023
Original language	American English
Awarding Institution	HBKU College of Health & Life Sciences