Non-motor symptoms of PD revealed in mice with reduced vesicular storage Tonya Taylor MSP Symposium May 29, 2009

Overview of Parkinson’s Disease 2 nd most common neurodegenerative disorder Characterized by degeneration of DA neurons in the SNpc, subsequent loss of DA in the striatum, and presence of Lewy bodies Caused by genetic and environmental factors Tremor, rigidity, postural instability, bradykinesia Anosmia, sleep disturbances, depression, GI dysfunction

Characterization of VMAT2 LO mice Caudle, et al J. Neurosci 2007

VMAT2-deficient mice display widespread reductions in monoamines at months of age Taylor, et al J. Neurosci in press

VMAT2-deficient animals display reduced TH/TrpH expression and neurodegeneration at 24 months of age

Hypothesis: Reduced monoamine storage results in altered neurotransmission leading to the development of symptoms associated with PD

VMAT2 LO animals display progressive deficits in olfactory discrimination Taylor, et al J. Neurosci in press

VMAT2 LO animals display normal circadian activity but a premature shortened latency to behavioral signs of sleep Taylor, et al J. Neurosci in press

VMAT2 LO mice display altered gastric motility Taylor, et al J. Neurosci in press

VMAT2 LO animals display an anxiety-like and a progressive depressive-like phenotype Taylor, et al J. Neurosci in press 4-6 months12-15 months FST TST

VMAT2 LO mice exhibit motor deficits at older ages

Conclusions and Future Directions Reduced vesicular storage of monoamines reproduces many of the non-motor symptoms associated with PD – at advanced ages, reproduces motor phenotype Potential model for therapeutic intervention for non-motor symptoms – Antidepressant therapy? – Monoamine precursors?

Acknowledgements Miller Lab Dr. Gary Miller Kennie Shepherd, PhD Jodi Watson, BSN, MS Minzheng Wang, MD Yingjie Li, MD Danielle Dean, MS Stephen Hasak, MPH David Kopp, MPH Dana Annerino Brian Wojeck Weinshenker Lab Dr. David Weinshenker Jesse Schank, PhD Heather Mitchell Greene Lab Dr. James Greene AliReza Noorian, MD Iuvone Lab Dr. P. Michael Iuvone Nikita Pozdeyev, PhD Chad Jackson University of Washington W. Michael Caudle, PhD Committee Members Dr. James Greene Dr. Jason Hansen Dr. Yoland Smith Dr. David Weinshenker Funding NRSA F31 ES Emory Graduate Diversity Fellowship