Title

Effects of cell-specific MeCP2 expression on aggression using Drosophila as a model system for human disease

Presentation Type

Presentation

Abstract

Sporadic mutations in methyl-CpG-binding protein 2 (MeCP2) cause Rett Syndrome a severe, neurodevelopmental disorder characterized by loss of motor and language skills, unusual stereotyped movements, autistic features, anxiety, and an increase in aggression. Duplication of the MeCP2 gene in males results in multiple symptoms including mental retardation, autistic behaviors, stereotyped hand movements and anxiety-related behaviors. Although MeCP2 protein is found at high levels in essentially all cells in the nervous system, changes in neuronal or glial (support) cell MeCP2 expression may be responsible for the disease phenotypes. The heightened anxiety or aggression seen in people with MeCP2 disorders suggests neurons regulating moods such as serotonin, dopamine, or noradrenaline neurons may be involved. Using the UAS-Gal4 binary expression system we are able to express MeCP2 in both Drosophila octopamine neurons (the invertebrate equivalent of noradrenaline) and astrocytes (glial cells) separately. I am examining the effects of MeCP2 on the function of octopamine neurons in aggressive behavior. In Drosophila, aggression is a robust innate behavior comprised of reproducible, easily identifiable behavioral patterns. Two male flies of the same genotype are placed in a fight chamber, to compete for territory and food. After the fight, aggression is quantified by scoring the latency to aggression (time to first encounter), number of lunges (the predominant aggressive behavior), and percentage of trials that exhibit aggressive behavior. Because interactions between glia and neurons are essential for many critical brain functions, we propose that MeCP2 activity in astroctyes causes gene expression changes that change the function of neighboring neurons. I have observed increased latency to aggression and decreased lunges in flies expressing MeCP2 in OA neurons and in flies expressing MeCP2 in astrocytes. My results may be extrapolated to human beings via conserved cellular mechanisms.

Category

Life Sciences

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Apr 13th, 2:20 PM Apr 13th, 2:40 PM

Effects of cell-specific MeCP2 expression on aggression using Drosophila as a model system for human disease

UC 327

Sporadic mutations in methyl-CpG-binding protein 2 (MeCP2) cause Rett Syndrome a severe, neurodevelopmental disorder characterized by loss of motor and language skills, unusual stereotyped movements, autistic features, anxiety, and an increase in aggression. Duplication of the MeCP2 gene in males results in multiple symptoms including mental retardation, autistic behaviors, stereotyped hand movements and anxiety-related behaviors. Although MeCP2 protein is found at high levels in essentially all cells in the nervous system, changes in neuronal or glial (support) cell MeCP2 expression may be responsible for the disease phenotypes. The heightened anxiety or aggression seen in people with MeCP2 disorders suggests neurons regulating moods such as serotonin, dopamine, or noradrenaline neurons may be involved. Using the UAS-Gal4 binary expression system we are able to express MeCP2 in both Drosophila octopamine neurons (the invertebrate equivalent of noradrenaline) and astrocytes (glial cells) separately. I am examining the effects of MeCP2 on the function of octopamine neurons in aggressive behavior. In Drosophila, aggression is a robust innate behavior comprised of reproducible, easily identifiable behavioral patterns. Two male flies of the same genotype are placed in a fight chamber, to compete for territory and food. After the fight, aggression is quantified by scoring the latency to aggression (time to first encounter), number of lunges (the predominant aggressive behavior), and percentage of trials that exhibit aggressive behavior. Because interactions between glia and neurons are essential for many critical brain functions, we propose that MeCP2 activity in astroctyes causes gene expression changes that change the function of neighboring neurons. I have observed increased latency to aggression and decreased lunges in flies expressing MeCP2 in OA neurons and in flies expressing MeCP2 in astrocytes. My results may be extrapolated to human beings via conserved cellular mechanisms.