Research Projects

Completed research projects 2005-2009

1. “Validation of mGluR5 antagonism in non-human primates as a treatment for L-DOPA-induced dyskinesia" 
Funding agency: M J Fox Foundation for Parkinson’s Research Period: 2008-2009 Principal investigators: Cenci Nilsson and Bezard (Co-PIs)

Brief Abstract: This project has validated the efficacy of selective antagonists of metabotropic glutamate receptor type 5 (mGluR5) as a treatment for L-DOPA-induced dyskinesia in a non-human primate model of Parkinson's disease.

2. “Neoangiogenesis in L-DOPA-induced dyskinesia" 
Funding agency: M J Fox Foundation for Parkinson’s Research Principal Investigator: Cenci Nilsson Period: 2006-2008

Brief Abstract: This project has shown that treatment with L-DOPA causes endothelial proliferation and microvessel elongation (angiogenesis) in the parkinsonian brain, associated with an increased blood-brain barrier permeability. These microvascular changes correlate with the development of motor complications to the treatment (dyskinesia)

3. "Two-photon microscopy for studies of cellular dynamics" 
Funding agency: Swedish Research Council Principal Investigator: Cenci Nilsson Period: 2007-2009

Brief Abstract: This grant has provided funding for capital equipment for Dr. Cenci’s and other laboratories within the Neurofortis consortium. The purchased equipment will enable these groups to use advanced laser scanning microscopy in order to study dynamic cellular alterations in rodent models of neurological disease.

4. Dyskinesias in Parkinson´s Disease: cellular mechanisms and novel treatment options 

Principal Investigator: M.A. Cenci
Funding Agencies: Swedish Research Council, Thorsten och Elsa Segerfalks Foundation, Greta and Johan Kock Foundation, King Gustaf V and Queen Victoria Foundation, The Swedish Parkinson Foundation

Brief Abstract: A broad range of biochemical, cellular, and molecular investigations on the basal ganglia in rat and mouse models of Parkinson´s disease and L-DOPA-induced dyskinesia. These studies encompass analyses of activated protein kinases, gene and protein expression, cell genesis, energy metabolism and transmitter release. Some of the findings obtained in rodent models are verified in human post-mortem brains by immunohistochemical analysis of disease markers.

Principal Investigator: M.A. Cenci
Funding agency: Merz Pharmaceuticals, Frankfurt (Germany)

Brief Abstract: Striatal protein extracts from dyskinetic rats and nondyskinetic controls are studied using two-dimensional gel electrophoresis followed by mass-spectrometric analyses. The most important results are validated using Western immunoblotting and immunohistochemical techniques.

5. Dopamine release and metabolism in animal models of neurodegenerative disease 

Principal Investigator: M.A. Cenci

Funding agencies: Thorsten and Elsa Segerfalks Foundation; The Swedish Parkinson Foundation; The Crafoord Foundation

Brief Abstract: This equipment grant has allowed us to set up the intracerebral microdialysis technique and analytical methods for the measurement of catecholamines here at Wallenberg Neuroscience Centre. This equipment is now used by several research groups in order to study the release and metabolism of catecholamines in rodent models of Parkinson´s Disease, L-DOPA-induced dyskinesia, and Huntington´s release.

6. Role of the Ras/ERK signaling pathway in the development of dyskinesia and motor fluctuations during chronic L-DOPA treatment 

Principal Investigators: Cenci M.A. and Brambilla R. (San Raffaele Inst., Milano, I)
Funding agency: The M.J. Fox Foundation for Parkinson´s Research

Brief abstract: This study addresses tbe importance of Ras-dependent activation of extracellular regulated kinases 1 and 2 (ERK1/2) for the development of L-DOPA-induced dyskinesia and motor fluctuations. For these experiments, we utilize both wild-type mice and transgenic mice that either lack or overexpress critical regulators of Ras/ERK signaling.

7.  Metabotropic glutamate receptors in L-DOPA-induced dyskinesia 

Principal Investigator: M.A. Cenci
Funding agency: The M.J. Fox Foundation for Parkinson´s Research

Brief Abstract: This study aims at evaluating the antidyskinetic and antiparkinsonian potential of novel compounds that act as either antagonists of metabotropic receptors-group I or as agonists of metabotropic receptor-group II.

8. Mechanisms of graft-induced dyskinesia in a rat model of Parkinson´s disease 

Principal Investigators: M.A. Cenci and P. Brundin
Funding Agency: The Michael J Fox Foundation for Parkinson´s Research

Brief abstract: Our project aims at developing a model of graft-induced dyskinesia (GID) in the rat,which will be used for studying the mechanisms of this movement disorder.

9. Levodopa Dyskinesia and Striatal Neuroplasticity 

Principal Investigator: Christine Konradi (McLean Hospital, Harvard Medical School, Belmont MA); (M.A. Cenci subcontractor in Lund, Sweden)
Funding Agency: National Institute of Neurological Disorders and Stroke, USA

Brief abstract: Following gene-array analysis of striatal mRNA from Parkinson patients (by Konradi´s group), Cenci´s group will dissect the importance of specific genes for the development of L-DOPA-induced dyskinesia in rodent models.