MOVEMENT DISORDERS A · The implications and interactions of basal ganglia and cerebellum in movement disorders
FP6 — Marie Curie Actions (Human Resources and Mobility)
- Duration
- 2004-06-15 → 2005-06-14
- EU contribution
- €39,175
- Participants
- 1
- Scheme
- ERG
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Results in brief
Final Activity Report Summary - MOVEMENT DISORDERS A (The implications and interactions of basal ganglia and cerebellum in movement disorders)
First microdialysis experiments were conducted in anaesthetised naive rats to assess the effect of a microinjection with the GABA antagonist bicuculline in the dentate nucleus, a main output nucleus of the cerebellum, on glutamate and GABA release in the centrolateral nucleus and the dorsal striatum. This microdialysis approach was completed by the simultaneous detection of DA and the metabolites 3,4-dihydroxyphenylacetic and homovanillic acid in the dorsal striatum. The preliminary results show that an inhibition of the dentate nucleus does not modulate the release of glutamate and GABA in the centrolateral nucleus and the dorsal striatum, while DA transmission in the dorsal striatum is increased. This suggests that the cerebellar output nuclei might modulate the activity of nigrostriatal dopamine neurons although the implicated pathways remain yet unknown. Interestingly, these nigrostriatal dopamine neurons undergo a progressive degeneration in PD suggesting that the cerebellum could be implicated in the onset of PD symptoms or compensatory mechanisms in the course of the disease. In a second part of the project and in collaboration with the research group of Professor A. Kupsch, a microstimulator has been developed that allows the application of continuous high frequency stimulation in rats for several weeks. This device will be mandatory in the future to determine mechanisms of action of high frequency stimulation implicating BG and cerebellum.
Data: CORDIS, © European Union
Project objective
The proposed project is designed to investigate the implication and interaction of the basal ganglia (BG) and the cerebellum in different movement disorders. Beyond the role attributed to the BG in the pathophysiology of movement disorders, the cerebellum is also known to be involved in motor control and non-motor tasks such as mental imagery, sensory processing, planning, attention and language. However, the exact mechanisms such a control under normal and pathophysiological conditions are not clear. Studi es in patients suffering from Parkinson's disease (PD) using positron emission tomography have suggested the implication and interaction of both the cortico-BG-thalamocortical loop and the cerebello-thalamocortical pathway in the pathophysiology of PD. Mor eover, compensatory mechanisms delaying the onset of PD symptoms are expected to reside in the cerebello-thalamocortical pathway. Beyond the implication of the cerebellum in the pathophysiology of PD, it has been reported that modifications in cerebellar a ctivity also occur in other movement disorders such as multiple system atrophy (MSA), dystonia, Huntington's disease (HD) and essential tremor. The objectives are (i) to understand the implication and interaction of BG and cerebellum in different movement disorders such as PD, MSA, dystonia and HD, (ii) to identify compensatory mechanisms residing in cerebello-thalamocortical pathways and (iii) to determine mechanisms of action of high frequency stimulation implicating BG and cerebellum. These objectives wi ll be achieved using complementary techniques (2-deoxyglucose activity, in situ hybridisation of different neuronal markers, microdialysis and HPLC). In the longer term, these techniques will be extended by extracellular multi¬ channel recordings and beha viour (motor and cognitive component tasks). The expected results will improve our pathophysiological comprehension of disabling movement disorders with high socio-#
Original text from CORDIS.
Participants
- HUMBLODT UNIVERSITAET ZU BERLIN - UNIVERSITAETSKLINIKUM CHARITE · BERLINCoordinatorCity levelGermany
Links
Data: CORDIS, © European Union