title: Behavioral and histological analysis of a partial double-lesion model of parkinson-variant multiple system atrophy.
abstract: Multiple system atrophy (MSA) is a neurodegenerative disease with progressive autonomic failure, cerebellar ataxia (MSA-C), and parkinsonism (MSA-P) resulting from neuronal loss in multiple brain areas associated with oligodendroglial cytoplasmic α-synuclein inclusion bodies. No effective treatments exists, and MSA-P patients often fail to respond to L-DOPA because of the loss of striatal dopaminergic receptors. Rendering MSA-P patients sensitive to L-DOPA administration following striatal tissue transplantation has been proposed as a possible novel therapeutic strategy to improve the clinical condition. Here we describes simple, skilled, and sensorimotor behavior deficits in a unilateral partial double-lesion (DL) rat model of MSA-P. The sequential striatal double-lesion model mimicks early MSA-P pathology by combining partial 6-hydroxydopamine (6-OHDA) followed by striatal quinolinic acid (QA) lesion. Animals were tested on spontaneous, learned, or drug-induced behavioral tasks on multiple occasions pre- and postsurgery. The data show robust, lateralized deficits, and the partial 6-OHDA and the double-lesioned animals were most impaired. Importantly, this study identified a behavioral deficit profile unique to the double-lesion animals and distinctive from the single 6-OHDA- or the QA-lesioned animals. Histology confirmed an approximately 40% dopamine loss in the striatum in the 6-OHDA and double-lesion animals as well as a similar loss of striatal projection neurons in the QA and double-lesion animals. In summary, we have established the behavioral deficit profile of a partial double-lesion rat model mimicking the early stage of MSA-P.
authors.affiliation: Neurological Research Laboratory, University Hospital, Innsbruck, Austria.
authors.forename: Christine
authors.initials: C
authors.lastname: Kaindlstorfer
authors.forename: Joanna
authors.initials: J
authors.lastname: García
authors.forename: Christian
authors.initials: C
authors.lastname: Winkler
authors.forename: Gregor K
authors.initials: GK
authors.lastname: Wenning
authors.forename: Guido
authors.initials: G
authors.lastname: Nikkhah
authors.forename: Máté D
authors.initials: MD
authors.lastname: Döbrössy
mesh_terms: D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D002452:Cell Count; D003342:Corpus Striatum / Q000293:injuries*; D004195:Disease Models, Animal; D018491:Dopamine Agonists / Q000494:pharmacology; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32 / Q000378:metabolism; D005106:Exploratory Behavior / Q000187:drug effects; D005260:Female; D007839:Functional Laterality; D020233:Gait Disorders, Neurologic / Q000209:etiology*; D009043:Motor Activity / Q000187:drug effects; D019578:Multiple System Atrophy / Q000139:chemically induced / Q000150:complications* / Q000473:pathology*; D016627:Oxidopamine / Q000633:toxicity; D010300:Parkinson Disease / Q000150:complications* / Q000209:etiology / Q000473:pathology*; D011597:Psychomotor Performance / Q000187:drug effects; D017378:Quinolinic Acid / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D018491:Dopamine Agonists; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; C497930:Ppp1r1b protein, rat; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; D017378:Quinolinic Acid; D001058:Apomorphine