title: Development of an Alpha-synuclein Based Rat Model for Parkinson's Disease via Stereotactic Injection of a Recombinant Adeno-associated Viral Vector.
abstract: In order to study the molecular pathways of Parkinson's disease (PD) and to develop novel therapeutic strategies, scientific investigators rely on animal models. The identification of PD-associated genes has led to the development of genetic PD models. Most transgenic α-SYN mouse models develop gradual α-SYN pathology but fail to display clear dopaminergic cell loss and dopamine-dependent behavioral deficits. This hurdle was overcome by direct targeting of the substantia nigra with viral vectors overexpressing PD-associated genes. Local gene delivery using viral vectors provides an attractive way to express transgenes in the central nervous system. Specific brain regions can be targeted (e.g. the substantia nigra), expression can be induced in the adult setting and high expression levels can be achieved. Further, different vector systems based on various viruses can be used. The protocol outlines all crucial steps to perform a viral vector injection in the substantia nigra of the rat to develop a viral vector-based alpha-synuclein animal model for Parkinson's disease.
authors.affiliation: Laboratory for Neurobiology and Gene Therapy, Department of Neurosciences, KU Leuven.
authors.forename: Anke
authors.initials: A
authors.lastname: Van der Perren
authors.affiliation: Division of Nuclear Medicine, Leuven University Hospital - KU Leuven.
authors.forename: Cindy
authors.initials: C
authors.lastname: Casteels
authors.affiliation: Division of Nuclear Medicine, Leuven University Hospital - KU Leuven.
authors.forename: Koen
authors.initials: K
authors.lastname: Van Laere
authors.affiliation: Laboratory for Molecular Virology and Gene Therapy, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven; Leuven Viral Vector Core, KU Leuven.
authors.forename: Rik
authors.initials: R
authors.lastname: Gijsbers
authors.affiliation: Laboratory for Neurobiology and Gene Therapy, Department of Neurosciences, KU Leuven; Leuven Viral Vector Core, KU Leuven.
authors.forename: Chris
authors.initials: C
authors.lastname: Van den Haute
authors.affiliation: Laboratory for Neurobiology and Gene Therapy, Department of Neurosciences, KU Leuven; veerle.baekelandt@med.kuleuven.be.
authors.forename: Veerle
authors.initials: V
authors.lastname: Baekelandt
mesh_terms: D000818:Animals; D000229:Dependovirus / Q000235:genetics; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000378:metabolism; D005260:Female; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000008:administration & dosage; D007267:Injections; D008822:Mice, Transgenic; D010300:Parkinson Disease / Q000235:genetics*; D017208:Rats, Wistar; D013378:Substantia Nigra / Q000378:metabolism; D019076:Transgenes / Q000235:genetics; D051844:alpha-Synuclein / Q000235:genetics*
chemical_list: C497606:Snca protein, rat; D051844:alpha-Synuclein; D004298:Dopamine