Date of Award

2016

Document Type

Honors Thesis (Colby Access Only)

Department

Colby College. Biology Dept.

Advisor(s)

S Tariq Ahmad

Abstract

Circadian rhythms govern the 24-hour sleep-wake cycle found in most organisms including humans and Drosophila. Patients with frontotemporal dementia (FTD) commonly experience deficits in circadian rhythm functioning. To investigate the basis of this, I misexpressed a mutant isoform of the charged multivesicular body protein 2B (CHMP2BIntron5) found in human FTD patients in two subsets of the Drosophila circadian pacemaker neurons (CPNs) using the GAL4-UAS system. The first subset targeted were CPNs responsible for the morning activity period (pdf-GAL4) and the second for morning and evening activity periods (cry-GAL4). Using this model and genetic ablation models I was able to assess the circadian activity of flies as well as image the brains of these flies while fluorescently marking the CPNs. Through these experiments I observed that CHMP2BIntron5 expressed in Pdf or Cry CPNs resulted in loss of morning activity without causing cell death. I furthermore observed the absence of a morning period caused by ablating pdf cells and the absence of both morning and evening peaks resulting in arrhythmic behavior caused by ablating cry cells. This indicates a heightened sensitivity to CHMP2BIntron5 pathology in the Pdf morning cells. Molecular analyses to determine what is causing this disruption are forthcoming.

Keywords

FTD, Dementia, Circadian Rhythms, Drosophila

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