Biological bases of PD subtypes

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Table of contents

Remerciements
Table of contents
List of abbreviations
List of figures
Résumé en français
INTRODUCTION
CHAPTER 1 – PARKINSON’S DISEASE
A. Symptomatology
1. Motor symptoms
2. Psychiatric symptoms
3. Other non-motor symptoms
4. Heterogeneity and subtypes
B. Biological bases
1. Genetic and environmental factors
2. Cellular pathology
3. Progression mechanisms
4. Brain-wide effects
5. Associations with the psychiatric symptoms
6. A focus on the basal ganglia
C. Treatments
CHAPTER 2 – GPR88
A. Studies of Gpr88
1. Characteristics
2. Insights into Gpr88 function
3. Gpr88 as a therapeutic target
B. Relevance to Parkinson’s disease
CHAPTER 3 – THE RESEARCH PROJECT
A. Objectives
B. Modeling Parkinson’s disease in rats
1. The 6-OHDA toxin
2. Modeling the motor symptoms
3. Modeling the psychiatric symptoms
C. Lentiviral-mediated Gpr88 knockdown
1. The basis: engineered RNA interference
2. The delivery: lentiviral vectors
4 RESULTS
ARTICLE 1 Manuscript : Knock-down of GPR88 alters the response of medium spiny neurons to loss of DA input and L-DOPA.
ARTICLE 2 Manuscript : Gpr88 knock-down in the associative striatum reduces the psychiatric symptoms in a model of Parkinson’s Disease.
GENERAL DISCUSSION
A. Validating Gpr88 as a therapeutic target for Parkinson’s disease
1. Main findings
2. Limitations and future directions
B. Striatal dynamics in basal ganglia disorders
1. Striatal imbalances
2. Biological bases of striatal shifts
3. Therapeutic targeting of the DMS/DLS imbalance
General conclusion
REFERENCES