Page 18 - ACHEMS 2012 PROGRAM

18 | AChemS Abstracts 2012 Abstracts are printed as submitted by the author(s)
#26 SYMPOSIUM:
CHEMICAL SENSES IN HEALTH & DISEASE
Sensory Alterations in Early Parkinson’s Disease
Richard L. Doty1,2, Allen Osman1,2, Emma Harmon1,2, Jacob
Dubroff1,3, Jennifer Rotz1,2, Michele Morris1,2, James Wilson1,4,
Fidias E. Leon-Sarmiento1,2, Andrew Siderowf1,4, Laura Balcer1,4,
Andrew Newberg1,3, Paul Moberg1,5, Bruce Turetsky 1,5,
James W. Hall1,6, Neil Shepard1,7, Gui-Shang Ying1,4
1Smell & Taste Center, University of Pennsylvania Philadelphia,
PA, USA, 2Department of Otorhinolarygnology: Head & Neck
Surgery, University of Pennsylvania Philadelphia, PA, USA,
3Department of Radiology, University of Pennsylvania
Philadelphia, PA, USA, 4Department of Neurology, University of
Pennsylvania Philadelphia, PA, USA, 5Department of Psychiatry,
University of Pennsylvania Philadelphia, PA, USA, 6Department of
Speech, Language and Hearing Sciences, University of Florida
Gainesville, FL, USA, 7Department of Otolaryngology, Mayo Clinic
Rochester, MN, USA
Olfactory dysfunction is an early ‘pre-clinical’ sign of Parkinson’s
disease (PD). Other sensory disturbances, including alterations in
taste and vision, have also been reported in early PD. In this
presentation, an overview of the influences of PD on the function
of olfaction and the other major senses is provided. Early results
are presented from an ongoing study of the administration of a
large battery of sensory tests to the same cohort of early stage PD
patients while on and off of dopamine therapy. In addition to
SPECT imaging of the dopamine transporter, the subjects of this
study were administered the following sensory tests:
olfaction: odor identification, detection, discrimination/memory,
suprathreshold intensity and pleasantness, sniff magnitude, odor
event-related potential; taste: whole-mouth taste identification;
chemical and electrical regional chemosensory tests; touch: spatial
and point tactile thresholds; hearing: pure-tone thresholds; filtered
words test; auditory figure-ground test; competing words test;
competing sentences test; hearing in noise (HINT) test; gaps in
noise (GIN) test, auditory brainstem and cortical electrical
responses; vision: visual acuity; contrast sensitivity; color vision
testing; optical coherence tomography (OCT); pattern visual
evoked potentials (PVEP); pattern electroretinography (PERG);
balance: computerized dynamic posturography, oculomotor
testing, and caloric studies. Preliminary findings suggest that
olfaction and taste discriminate better between PD patients and
controls than other sensory measures and discriminate as well or
better than SPECT imaging of the dopamine transporter.
Dopaminergic therapy appears to have little influence on any
of the test measures. Acknowledgements: USAMRAA
W81XWH-09-1-0467
#27 SYMPOSIUM:
CHEMICAL SENSES IN HEALTH & DISEASE
Modulation Of Airway Defense Functions From Environmental
Chemical Exposure
Pamela Dalton
Monell Chemical Senses Center Philadelphia, PA, USA
The chemosensory systems in the nose and upper airways serve a
critical protective role — not only to detect but also to trap, clear
and detoxify many inhaled exogenous pollutants. However, the
capacity of these defense mechanisms in the airways can be
overwhelmed by significant acute or chronic exposures. Exposure-
induced inflammation and morphological changes can lead to
altered olfactory and nasal trigeminal sensitivity. Moreover, the
interaction of such exposures with individual susceptibility factors,
such as tobacco use, nasal metabolic capacity and pre-existing
inflammatory disease can predispose individuals to additional
damage to the airways. This talk will review clinical studies in
pollutant-exposed populations, including those exposed on 9/11 and
beyond at the World Trade Center, and discuss the implications for
the observed changes and potential for recovery in chemosensory
function. Acknowledgements: NIH-NIDCD P50 DC 006760
#28 PLATFORM PRESENTATIONS —
POLAK YOUNG INVESTIGATOR AWARD WINNERS
Olfactory Behavior Correlates with APP-induced Circuit
Disruption and Recovery
Ning Cheng, Leonardo Belluscio
NIH/NINDS Bethesda, MD, USA
Neural circuits are precisely organized; however, the relation
between correct wiring and behavior is poorly understood.
Knowledge of this association would be useful to assess functional
recovery from disease. We recently established a reversible
olfactory-based disease model in which OSNs can be rapidly
induced to degenerate by overexpressing amyloid precursor protein
(APP), which is critically involved in Alzheimer’s disease. Using
this model we found that OSNs undergo extensive apoptosis by
3-weeks of age and without the presence of extracellular amyloid
deposits. Here we show that APP was also present in OSN axons,
which showed strong caspase3 signal and reduced synaptic protein
expression. We found that glomerular structure was severely
distorted in mutant mice and that OSN axonal convergence was
disrupted. Using SpH-imaging we further revealed that odor-
induced activity was much diminished in the OB consistent with
anatomical findings. We further show using behavioral assays that
olfactory detection and discrimination was significantly impaired.
Since OSNs are known to continuously regenerate we tested the
capacity of the system for restoration following APP-induced
disruption. We reveal that within 1 week after shutting-off APP
expression, the glomerular circuitry was partially restored both in
structure and function and that behavioral deficits were similarly
reversed. Together, these data show a clear correlation between
functional recovery and circuit organization, suggesting that while
precise wiring may be necessary for optimal function, basic
function can occur even if wiring is not completely correct. These
findings further support a cell autonomous role for APP in inducing
OSN degeneration, and present a model to study circuit disruption
and repair within a precisely defined network. Acknowledgements:
NIH intramural program 1ZIANS003002-09
O R A L A B S T R A C T S