Evaluation of Drug "X" in Preclinical Models of Parkinson's Disease
Parkinson's disease (PD) is a hypokinetic, age-related movement disorder associated with chronic, progressive degeneration of dopaminergic neurons, with cell bodies located in the substantia nigra pars compacta (SNpc) and axon terminals in the striatum. Striatal depletion of the neurotransmi...
| Main Author: | |
|---|---|
| Other Authors: | |
| Language: | en_US |
| Published: |
The University of Arizona.
2017
|
| Online Access: | http://hdl.handle.net/10150/625144 http://arizona.openrepository.com/arizona/handle/10150/625144 |
| Summary: | Parkinson's disease (PD) is a hypokinetic, age-related movement disorder associated with
chronic, progressive degeneration of dopaminergic neurons, with cell bodies located in the
substantia nigra pars compacta (SNpc) and axon terminals in the striatum. Striatal depletion of
the neurotransmitter dopamine (DA) gives rise to the cardinal PD motor symptoms. We utilized
a 6-hydroxydopamine (6-OHDA) animal PD model to test the application of a preclinical drug
candidate, drug "X", in ameliorating and/or preventing advanced parkinsonism in two studies.
First, a neurorestoration study tested the efficacy of drug "X" in restoring motor functionality to
animals in which the 6-OHDA lesion had fully developed. Second, a neuroprotection study
assessed the effectiveness of drug "X" in preventing the initial development of the 6-OHDA
lesion and the onset of motor impairments. Behavioral data indicate that there are no significant
differences between the control and drug "X" groups in both studies, suggesting that drug "X"
does not improve established severe PD motor deficits nor prevent their initial development.
However, we are analyzing brain tissue harvested to 1) verify the extent of the lesion with
stereology in the SNpc, 2) evaluate striatal DA levels, and 3) investigate any neuroprotective
effects of drug "X" on nigral DAergic neurons. |
|---|