Project Details
Abstract
Parkinson’s disease (PD) is the second common neurodegenerative disease among the
elderly which reflects ongoing nigrostriatal dopaminergic degeneration. The pathology of PD
is characterized by the accumulation of Lewy body inclusions in dopaminergic neurons which
become a critical pathological hallmark of the idiopathic PD. Several evidences have
converged to suggest that failure of the ubiquitin-proteasome system to remove unwanted
proteins plays a major role in the etiopathogenesis of PD.
For purposes in developing novel pharmacological approaches to therapy, in creating
new treatment strategies and in understanding the nature of the pathogenic processes involved
in neuronal loss, there has been a key role for animal models of PD. The long been used
6-OHDA- and MPTP-treated animal models of PD fail to truly reflect the widespread and
progressive pathology of the illness, such as the formation of Lewy bodies and the presence of
activated microglial cells. A selective proteasom inhibitor, lactacystin, has been used to
induce PD model in rodents with the presence of -synuclein aggregations in the brain.
While the nigrostriatal neuropathology of lactacystin-treated rat brain has been studied
with MRI, the distributions of neuronal membrane dopamine transporters (DAT) and vesicular
monoamine transporters type 2 (VMAT2) in lactacystin-induced PD models have nerver been
evaluated yet.
In this three-year project, a rat model of PD induced by treatment with various
intracranial injection doses of lactacystin will be established. Two radiotracers,
[18F]FP-(+)DTBZ and [123/125I]FP-CIT will be used to evaluate the distributions of VMAT2
and DAT in lactacystin-treated rat brain by using microPET, microSPECT and
autoradiography imaging modalities, respectively. The molecular imaging will be extended to
examine if [18F]FP-(+)DTBZ PET and [123I]FP-CIT SPECT imaging reflect neurotrophic
factor restored dopaminergic neurons in lactacystin-induced rodent model.
Project IDs
Project ID:PC10401-0209
External Project ID:NSC102-2314-B182-049-MY3
External Project ID:NSC102-2314-B182-049-MY3
Status | Finished |
---|---|
Effective start/end date | 01/08/15 → 31/07/16 |
Keywords
- Parkinson’s disease
- rat model
- lactacystin
- [18F]FP-(+)DTBZ
- [123/125I]FP-CIT
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