Objective/Rationale:
Parkinson’s disease is widely attributed to neuropathy of dopaminergic neurones in the nigrostriatal (NS) pathway. Degeneration of noradrenergic and serotonergic neurones in the brain may actually precede the DA lesion but has received comparatively little attention. Damage to all these neuronal systems would contribute to comorbid anxiety, depression and cognition deficits in PD. However, these deficits have received comparatively little attention. The aim of this project is to develop and validate neurochemical/behavioural models that will allow a greater understanding of these non-dopaminergic deficits with the future aim of improved treatment.
Project Description:
The non-motor symptoms of PD include anxiety, depression and decreased cognitive abilities. Collectively, although not as overt as the motor symptoms, these effects significantly decrease quality of life for many PD patients. Here we intend to develop rodent models to simulate, as far as reasonably possible, neurological equivalents of the situation in patients. This will be accomplished by the use of selective neurotoxins to mimic the ‘non-motor’ pathology documented in PD. Much of the work will go into developing these models after which we hope to measure simple behaviours commonly utilized as indices of mood and cognition. It is also intended to study in detail the neurochemical changes which occur in these rodents in order to gain greater insight into how far these appear to reflect the human condition.
Relevance to Diagnosis/Treatment of Parkinson’s Disease: Generation of models which mimic the non-motor symptoms of PD constitute a relatively unstudied but important field. Robust animal models form a key substrate through which novel compounds may be tested. Although animal models are frequently criticized for failing to mimic PD in the clinic, there are as yet no obvious alternatives to this strategy. Therefore, the development of novel models to study ‘emotional’ and cognitive aspects of PD will make a valuable addition through which the lives of patients may be improved.
Anticipated Outcome:
We are confident that we can generate models for the non-motor symptoms of PD. The work on this project will be performed by the applicants themselves with support from a postdoctoral research fellow currently working in Dr. Whitton’s laboratory. We would anticipate ascertaining the effects of NA/5-HT lesions on key losses observed during the neuropathology of PD of a non-motor nature. This will provide a potential base to study the efficacy/value of novel therapeutic substances on these parameters.