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Evaluation of a multiple system atrophy model in rats using multitracer microPET
Hyung Ho Yoon1, Chong Sik Lee, Seok Ho Hong
1Department of Neurological Surgery, Asan Medical Center, University of Ulsan College of Medicine, Songpa-gu, Seoul, Korea.
Acta Neurochirurgica
|August 26, 2011
Summary
This study shows that a double toxin-double lesion model can mimic multiple system atrophy-parkinsonism (MSA-p) pathology. However, standard behavioral tests are unreliable for long-term assessment in this animal model.
Area of Science:
- Neuroscience
- Animal Models
- Neurodegenerative Diseases
Background:
- Striatonigral degeneration, a key feature of multiple system atrophy (MSA), can be modeled using a double toxin-double lesion strategy.
- Accurate characterization of animal models is crucial before testing therapeutic interventions for MSA.
- A known limitation in existing double-toxin models is the transient recovery of motor function, masking the persistent pathology.
Purpose of the Study:
- To assess the long-term pathological and functional changes in a rat model of MSA-parkinsonism (MSA-p) using a double toxin-double lesion approach.
- To evaluate the efficacy of standard behavioral tests for monitoring disease progression in this MSA-p model.
- To investigate the underlying mechanisms of functional recovery observed in this model.
Main Methods:
- Wistar rats underwent 6-hydroxydopamine (6-OHDA) medial forebrain bundle lesions followed by quinolinic acid (QA) striatal injections.
- Apomorphine-induced rotation and rotarod tests were used to assess motor function.
- Positron emission tomography (PET) with [(18)F]-FDG and [(18)F]-FP-CIT, along with tyrosine hydroxylase (TH) and cresyl violet staining, were employed for pathological characterization.
Main Results:
- QA administration significantly reduced contralateral rotation, but this effect reversed within weeks, masking persistent pathology.
- Rotarod tests showed no significant difference between the Parkinson's disease (PD) and MSA-p states.
- MicroPET revealed persistent glucose hypometabolism and dopamine transporter (DAT) deficits, while histology confirmed nigral cell loss and striatal atrophy.
Conclusions:
- The double toxin-double lesion method successfully generates persistent pathological changes consistent with MSA-p.
- Standard behavioral tests, including drug-induced rotation and rotarod tests, are inadequate for long-term evaluation of this MSA-p model.
- Development of more sensitive and specific behavioral tests is necessary for accurate long-term follow-up in MSA-p animal models.
