Abstract Details

Title Olfactory Dysfunction and Cholinergic Neuron Alteration in Olfactory Bulb in Transgenic Mice Expressing Human A53T Mutant ?-Synuclein

Topic Movement Disorders

Presentation(s) P05 - (-)

Poster/Presentation
Number 057

Objective

Background BACKGROUND: PD has both motor and non-motor manifestation. Hyposmia is one of the earliest signs of PD occuring in more than 90% cases. There is no clear coherent view how hyposmia occurs in PD and what is the relationship between ?-synucleinopathy and hyposmia.

Design/Methods DESIGN/METHODS: We used h?Syn A53T tg mice to assess the olfactory and motor functions. We employed a series of olfaction tests (odor detection, odor discrimination, odor habituation and odor memory). We assessed the neuropathological changes of dopamineric, cholinergic, ?-Aminobutyric acidergic and glutaminergic neurons at the olfactory bulb and at the substantia nigra (SN). In additiona, we measured the ?-synuclein expression level and aggregation at the olfactory bulb and SN in the mice.

Results RESULTS: We found that the ?-synA53T tg mice expressed high level of ?Syn in brain and have no dopaminergic neuron loss in SN.We detected a deficit on odor discrimination and odor detection in the mice. Odor short-term memory/habituation was not different in tg mice from wt mice, but the tg mice displayed significant dysfunction on long-term memory. Most importantly, we demonstrated a significant decrease of cholinergic neurons in the mitral cell layer, and an increase of doapminergic neurons in the glomeruli layer of olfactory bulb in the tg mice. In addition,the tg mice had a significant reduction of acetylcholine esterase activity at the olfactory bulb.

Conclusions CONCLUSIONS: Our study indicates that the ?SynA53T mice can model hyposmia in PD. Although there is no obvious motor impairment in this mouse model, hyposmia appears to be an early non-motor symptom, and the cholinergic system defect in the olfactory bulb might be responsible for the olfactory dysfunction in PD.

Authors/Disclosures
PRESENTER	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
Gavin Giovannoni, MD (QMUL)	Dr. Giovannoni has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. Dr. Giovannoni has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Sanofi. Dr. Giovannoni has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Merck KGaA. Dr. Giovannoni has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Roche-Genentech. Dr. Giovannoni has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Moderna. Dr. Giovannoni has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sandoz. Dr. Giovannoni has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Astoria Biologica. Dr. Giovannoni has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Zenas. Dr. Giovannoni has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Giovannoni has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Giovannoni has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi. Dr. Giovannoni has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Medscape.

��ɫ��

��ɫ��