Molecular Imaging Study to Evaluate the Distributions of Dopamine Transporters and Type 2 Vesicular Monoamine Transporters in the Brains of Lactacystin-Induced Small Animal Models of Parkinson's Disease

  • Wey, Shiaw-Pyng (PI)
  • Chan, Ming Huan (CoPI)
  • Lin, Kun-Ju (CoPI)

Project: National Science and Technology CouncilNational Science and Technology Council Academic Grants

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
StatusFinished
Effective start/end date01/08/1531/07/16

Keywords

  • Parkinson’s disease
  • rat model
  • lactacystin
  • [18F]FP-(+)DTBZ
  • [123/125I]FP-CIT

Fingerprint

Explore the research topics touched on by this project. These labels are generated based on the underlying awards/grants. Together they form a unique fingerprint.