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Thesis Defense Presentation

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by

Sarah Dunalewicz

on 9 April 2015

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Transcript of Thesis Defense Presentation

Over 5 million patients in US
13.2 million by 2050
Almost $200 billion annually
$80,000 per year for caregivers
Alzheimer's Disease
Amyloid plaques- Beta-amyloid
Neurofibrillary Tangles (NFT)- tau protein
AD Pathology
www.brightfocus.org
coloradodementia.org
Tau and Tauopathies
Microtubule-associated protein
Hyperphosphorylated in AD and related tauopathies
Mutations characterize different tauopathies
FTDP17 characterized by R406W mutation
(Morris et al., 2011)
GAL4-UAS System
elav-GAL4: neuron-specific driver
UAS-tau: gene of interest
Effects of
Environmental Enrichment (EE)
Improves learning and memory in a mouse model of AD

Increases Neuroplasticity

Increases mating success in fruit flies

Higher concentration of Mushroom Body fibers in fruit flies
(Jankowski et al., 2005)
(Dukas & Mooers, 2003)
(Technau, 2007)
Transgenic Flies are Expressing Tau
Western Blot
Analysis
Fruit Fly Enrichment
Research Questions
1. Standard Vial Housing
Does EE affect tau toxicity?
Does EE affect tau phosphorylation?
Hypothesis: Environmental Enrichment will ameliorate tau toxicity and phosphorylation in a fly model of tauopathy.
2. Empty Arena:
Spatial stimulation
70x more vol./fly
3. EE Arena:
Spatial stimulation
Visual and tactile stimulation
EE Extends Control and Tau Fly Lifespan
Female Tau and Phosphorylation Levels are Equivalent
Male Tau and Phosphorylation Levels are Elevated
Conclusions
EE extended control and tau fly lifespan
EE ameliorated tau toxicity
EE increased tau phosphorylation in males
Sex-specific effects
Hormonal
Future Directions
Repeat lifespan experiments with separated sexes
Perform tau localization studies in Mushroom bodies
Address the effects of EE on heterochromatin relaxation
Acknowledgements
Thomas Liimatainen (MHC machinist)
MHC Department of Neuroscience
Ken Colodner
CLAN
The fruit flies

Sarah Dunalewicz
Honors Thesis
May 1, 2014

Investigating the Effects of Environmental Enrichment on a
Drosophila
Model of Tau Toxicity

(May, 2011)
Tau
Phosphorylation
Tau
Phosphorylation
N= 63-94
*** p<0.001
Proposed Mechanisms
N= 5-6
* p<0.05
N= 6
** p<0.01
Methods
N= 78-94
N= 63-89
N= 78-94
p= 0.369
N= 4-5
p= 0.982
N= 6
p= 0.628
Full transcript