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Behavioral and histological analysis of a partial double‐lesion model of parkinson‐variant multiple system atrophy
Author(s) -
Kaindlstorfer Christine,
García Joanna,
Winkler Christian,
Wenning Gregor K.,
Nikkhah Guido,
Döbrössy Máté D.
Publication year - 2012
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.23021
Subject(s) - lesion , quinolinic acid , parkinsonism , atrophy , striatum , oxidopamine , dopaminergic , neuroscience , pathology , parkinson's disease , medicine , dopamine , psychology , biology , substantia nigra , disease , tryptophan , biochemistry , amino acid
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. © 2012 Wiley Periodicals, Inc.