PgmNr D1287: Disruption of circadian rhythm through misexpression of a frontotemporal dementia-associated mutation in circadian pacemaker neurons in Drosophila.

Authors:
S. T. Ahmad; C. S. Krasniak; P. J. Kavaler

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Institutes
Colby College, Waterville, ME.

Keyword: circadian rhythms and sleep

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Abstract:

Frontotemporal dementia (FTD) is the second most common early-onset neurodegenerative disease. One subtype of FTD causes the production of CHMP2B^Intorn5, a mutant isoform of an ESCRT-III subunit. This causes disruptions in the autosomal-lysosomal and autophagy pathways. FTD patients show a variety of neurological symptoms, including disinhibition, apathy, aggressive behavior, and circadian rhythm deficits. To investigate these circadian rhythm deficits we ectopically expressed human CHMP2B^Intron5 using the GAL4-UAS system with the driver lines cry-GAL4 and pdf-GAL4 in Drosophila. These drivers are specific to an important subset of circadian pacemaker neurons in the brain. Using activity monitoring, we observed moderately disrupted circadian behavior. We did not observe any cellular death phenotype through whole brain imaging. To investigate the circadian deficits we are currently examining timeless and period transcript levels to investigate possible disruption of the molecular clock. This will allow us to further describe the circadian deficits caused by CHMP2B^Intorn5 misexpression.