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Poster Full Abstracts - Drosophila Models of Human Diseases
Poster board number is above title. The first author is the presenter
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whether
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and
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(Greene
et al
., 2003)
D. melanogaster
also model this phenotype. Literature addressing the potential protection by
nicotine in
Italic Text
D. melanogaster parkin
Italic Text
loss-of-function models spans limited concentrations of nicotine and selected time points and
durations in the organism’s lifespan. In order to more comprehensively address whether nicotine can protect against the various deficits in this model of
familial PD, we have assessed viability, olfaction, climbing and flying in wild-type,
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and
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D. melanogaster
that have been exposed to a
range of nicotine concentrations from eclosion until behavior assays are performed on days 5, 10 15 and 20 post-eclosion. Our results elucidate the
suitability of
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and
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/park
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in the pursuit of the mechanism(s) by which nicotine is protective against PD.
411C
Human LRRK2 expression increased animal lifespan and enhanced the resistance to oxidative stress in the Drosophila.
Hui-Yun Chang, Hung-Cheng
Wang, Franziska Wolter. Institute of Systems Neuroscience, National Tsing Hua University, Hsinchu, Taiwan.
We study the function of Leucine-rich repeat kinase 2 (LRRK2) in the animal model of Drosophila. LRRK2 mutations have been shown to be the most
common genetic causative effect to both familiar and sporadic forms of Parkinson's disease in human. However, little is known about its physiological
function in the animal brains. In this study, we found that LRRK2 expression in the brains showed an increase of the animal life span compared to normal or
driver alone in Drosophila. In addition, LRRK2 expression showed a protective effect to the environmental toxin of paraquat. Interestingly, LRRK2
expression could substantially suppress grim-induced apoptosis but not hid- and reaper- induced phenotypes in the fly eye. These data strongly support wild
type LRRK2 may play a role in protection from paraquat toxicity and neuronal degeneration.
412A
The role of Superoxide Dismutase 2 in a
Drosophila
model of Machado-Joseph Disease.
Natalie M. Clark, John M. Warrick. Department of Biology,
University of Richmond, Richmond, VA.
Spinocerebellar ataxia 3 (SCA3), also known as Machado-Joseph Disease (MJD), is an autosomal dominant neurodegenerative disorder caused by an
expanded polyglutamine repeat in the ataxin-3 protein. Research has suggested that MJD potentially increases the amount of reactive oxidative species
within the body, accelerating the cell aging process and increasing neural death. It is hypothesized that the increase of naturally occurring antioxidant gene
products such as Superoxide Dismutase 2 (SOD2) could decrease the severity of this disease and serve as a possible treatment. SOD2 is expressed in the
mitochondria, a likely location for increased reactive oxygen species. Mild, moderate, and strongly expressing UAS alleles of mutant and normal MJD as
well as UAS-SOD2 were expressed in the fly eye using the gmrGal4 driver. Flies were aged for one or seven days and their heads were fixed and embedded
in epon resin blocks. Ultramicrotome thin sections of fly retinas were evaluated using light microscopy. We found flies expressing both MJD and increased
levels of SOD2 had greater eye degeneration and faster progression of disease than flies with MJD and endogenous SOD2 levels. Additionally we examined
the influence of up regulated SOD2 on mutant MJD protein solubility. Other research has implicated superoxide in the autophagy pathway, and autophagy
has been suggested to reduce the degeneration caused by MJD by removing aggregates. Therefore, we propose that the increase in SOD2 levels interfered
with the autophagy pathway causing the increase in degeneration.
413B
The neurodegenerative AMPK mutant
loe
interferes with the RHO pathway and actin dynamics.
Mandy Cook, Jill Wentzell, Doris Kretzschmar.
CROET, Oregon Health and Science University, Portland, OR.
Isoprenylation is an important mechanism allowing intracellular proteins, like small G proteins (e.g. RHO) to associate with the membrane, which is then
followed by activation of the protein. This step is critical for signal transduction of cellular hormones, growth factors, and cytokines from the cytoplasm to
the nucleus and influences proliferation, differentiation and survival of the cell. The isoprenoid pathway is negatively regulated by AMPK (AMP- activated
protein kinase), an inhibitor of HMG-CoA Reductase (hydroxymethylglutaryl-CoA Reductase). The
Drosophila
mutant
loechrig
, which lacks a neuronal
isoform of the AMPK γ subunit, shows progressive neurodegeneration, neuronal cell death of the adult nervous system and a lower cholesterol ester level. In
order to determine the correlation between the
loe
mutation, isoprenylation and the RHO1 pathway, we generated and analyzed flies with mutations in RHO
and its downstream targets. We were able to show that the
loe
mutation interferes with the prenylation of RHO1 and the regulation of the downstream LIM-
Kinase pathway, which plays an important role in actin turnover and axonal remodeling. In addition, we used western blotting to show the concentration of
cofilin, which regulates actin turn over. Interestingly, all these defects including a behavior phenotype, can be detected before a severe neurodegeneration is
histologically visible.
414C
Characterizing mitochondrial dysfunction in a Drosophila model for TBI.
Vanessa T. Damm
1,2
, Rachel T. Cox
1,2
. 1) Biochemistry, Uniformed Services
University of the Health Sciences, Bethesda, MD; 2) Center for Neuroscience and Regenerative Medicine, Uniformed Services University of the Health
Sciences, Bethesda, MD.
Traumatic Brain Injury (TBI) affects millions of people every year, yet there is still much about the downstream molecular effects that we do not
understand. The primary injury from TBI is a devastating focal or diffuse injury to the brain caused by a blow to the head or shockwave, in the case of
combat. The resulting damage can lead to secondary injuries that result in subcellular changes and tissue damage. Our focus is on understanding the cell
biological changes post-injury that occur to mitochondria. An impact to the brain shears neuronal membranes which results in ionic misregulation, formation
of reactive oxygen species and calcium overload. This homeostatic disruption has a striking negative effect on mitochondrial function resulting in loss of
ATP production, dysregulated calcium storage, and apoptosis. In order to visualize the effects of TBI on mitochondria in real time, we are developing a TBI
model using the Drosophila larval brain. We have created transgenic flies expressing fluorescently labeled mitochondria, including those that sense reactive
oxygen species and calcium levels. We are using live confocal imaging to characterize mitochondrial dynamics in the larval brain pre- and post-injury. Once
we have established this TBI model, we hope to use it to identify neuroprotective genes and pathways. This knowledge may lead to better therapies
specifically designed to reverse mitochondrial damage post TBI.
415A