Reference : Effects of α-synuclein levels on cerebral synaptic function: Validation of a novel PE...
Scientific congresses and symposiums : Poster
Social & behavioral sciences, psychology : Neurosciences & behavior
http://hdl.handle.net/2268/177605
Effects of α-synuclein levels on cerebral synaptic function: Validation of a novel PET radioligand for the early diagnosis of Parkinson’s disease
English
Tarragon Cros, Ernesto mailto [Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biochimie et physiologie du système nerveux >]
Ferrara, André mailto [Université de Liège - ULiège > Département de Psychologie : cognition et comportement > Psychologie de l'apprentissage et cognition animale >]
Tirelli, Ezio mailto [Université de Liège - ULiège > Département de Psychologie : cognition et comportement > Neuroscience comportementale et psychopharmacologie expér. >]
Bahri, Mohamed Ali mailto [Université de Liège - ULiège > > Centre de recherches du cyclotron >]
Plenevaux, Alain mailto [Université de Liège - ULiège > > Centre de recherches du cyclotron >]
Garraux, Gaëtan mailto [Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biochimie et physiologie du système nerveux >]
27-Jan-2015
No
International
2015 GIGA day
27-01-2015
Université de Liège
Liège
Belgium
[en] alpha-synuclein ; microPET ; Parkinson's disease ; Preclinical model
[en] Background
In Parkinson’s disease, converging evidence supports a pathogenic role for excessive α–synuclein accumulation in synaptic terminals that may propagate back to the soma of vulnerable nerve cells such as neurons in the substantia nigra pars compacta. The resulting loss of dopaminergic terminals in the striatum can be demonstrated in vivo using 18F-Dopa-PET (positron emission tomography). However, there’s currently no validated biomarker of the progressive synaptic dysfunction in other vulnerable areas such as the cerebral cortex.
Goal
In this longitudinal study, we will test the hypothesis that the loss of synaptic terminals in a mouse model of excessive α–synuclein accumulation can be demonstrated in vivo before the occurrence of behavioural disturbances using 18F-UCB-H, a new PET biomarker developed at CRC. We will also test if this new imaging modality is sensitive enough to study the effect of a disease modifying therapy such as chronic physical exercise.
Methods
We will use microPET for the in vivo quantification of 18F-UCB-H brain uptake in 16 wild type animals and 16 transgenic (Tg) mice overexpressing human α–syn under the mThy1 promotor every 2 months. Data will be validated against post-mortem analyses after the last PET study.
Predictions
We predict decreased tracer uptake over time in the basal ganglia and cerebral cortex in Tg mice as compared with WT animals. Also, we predict a relationship between 18F-UCB-H uptake levels in basal ganglia and cerebral cortex and progressive alterations in both motor and cognitive functions, respectively. Further, we also expect that chronic exercise will slow down both motor and cognitive disturbances, as well as the rate of 18F-UCB-H brain uptake decreases.
Conclusion
If 18F-UCB-H PET proves to be a valid biomarker for the early detection of α–synuclein accumulation in the pre-clinical model of PD, the methods will tested on human clinical populations.
Centre de Recherches du Cyclotron - CRC ; Dépt. de Psychologie: cognition et comportament
Université de Liège ; MSCA-COFOUND BeIPD project framework
Researchers ; Professionals ; Students
http://hdl.handle.net/2268/177605

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