The Progressive BSSG Rat Model of Parkinson's: Recapitulating Multiple Key Features of the Human Disease
Identifieur interne : 000508 ( Main/Exploration ); précédent : 000507; suivant : 000509The Progressive BSSG Rat Model of Parkinson's: Recapitulating Multiple Key Features of the Human Disease
Auteurs : Jackalina M. Van Kampen [Canada] ; David C. Baranowski [Canada] ; Harold A. Robertson [Canada] ; Christopher A. Shaw [Canada] ; Denis G. Kay [Canada]Source :
- PLoS ONE [ 1932-6203 ] ; 2015.
English descriptors
- KwdEn :
- Animals, Brain (metabolism), Brain (pathology), Brain (physiopathology), Disease Models, Animal, Motor Activity (physiology), Neurons (metabolism), Neurons (pathology), Parkinson Disease, Secondary (metabolism), Parkinson Disease, Secondary (pathology), Parkinson Disease, Secondary (physiopathology), Rats, Rats, Sprague-Dawley, Sitosterols, alpha-Synuclein (metabolism).
- MESH :
- chemical , metabolism : alpha-Synuclein.
- chemical : Sitosterols.
- metabolism : Brain, Neurons, Parkinson Disease, Secondary.
- pathology : Brain, Neurons, Parkinson Disease, Secondary.
- physiology : Motor Activity.
- physiopathology : Brain, Parkinson Disease, Secondary.
- Animals, Disease Models, Animal, Rats, Rats, Sprague-Dawley.
Abstract
The development of effective neuroprotective therapies for Parkinson's disease (PD) has been severely hindered by the notable lack of an appropriate animal model for preclinical screening. Indeed, most models currently available are either acute in nature or fail to recapitulate all characteristic features of the disease. Here, we present a novel progressive model of PD, with behavioural and cellular features that closely approximate those observed in patients. Chronic exposure to dietary phytosterol glucosides has been found to be neurotoxic. When fed to rats,
Url:
DOI: 10.1371/journal.pone.0139694
PubMed: 26439489
PubMed Central: 4595214
Affiliations:
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Le document en format XML
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<front><div type="abstract" xml:lang="en"><p>The development of effective neuroprotective therapies for Parkinson's disease (PD) has been severely hindered by the notable lack of an appropriate animal model for preclinical screening. Indeed, most models currently available are either acute in nature or fail to recapitulate all characteristic features of the disease. Here, we present a novel progressive model of PD, with behavioural and cellular features that closely approximate those observed in patients. Chronic exposure to dietary phytosterol glucosides has been found to be neurotoxic. When fed to rats, <italic>β</italic>
-sitosterol <italic>β</italic>
-d-glucoside (BSSG) triggers the progressive development of parkinsonism, with clinical signs and histopathology beginning to appear following cessation of exposure to the neurotoxic insult and continuing to develop over several months. Here, we characterize the progressive nature of this model, its non-motor features, the anatomical spread of synucleinopathy, and response to levodopa administration. In Sprague Dawley rats, chronic BSSG feeding for 4 months triggered the progressive development of a parkinsonian phenotype and pathological events that evolved slowly over time, with neuronal loss beginning only after toxin exposure was terminated. At approximately 3 months following initiation of BSSG exposure, animals displayed the early emergence of an olfactory deficit, in the absence of significant dopaminergic nigral cell loss or locomotor deficits. Locomotor deficits developed gradually over time, initially appearing as locomotor asymmetry and developing into akinesia/bradykinesia, which was reversed by levodopa treatment. Late-stage cognitive impairment was observed in the form of spatial working memory deficits, as assessed by the radial arm maze. In addition to the progressive loss of TH<sup>+</sup>
cells in the substantia nigra, the appearance of proteinase K-resistant intracellular α-synuclein aggregates was also observed to develop progressively, appearing first in the olfactory bulb, then the striatum, the substantia nigra and, finally, hippocampal and cortical regions. The slowly progressive nature of this model, together with its construct, face and predictive validity, make it ideal for the screening of potential neuroprotective therapies for the treatment of PD.</p>
</div>
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<tree><country name="Canada"><noRegion><name sortKey="Van Kampen, Jackalina M" sort="Van Kampen, Jackalina M" uniqKey="Van Kampen J" first="Jackalina M." last="Van Kampen">Jackalina M. Van Kampen</name>
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