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Assessment of Sensorimotor Function in Mouse Models of Parkinson's Disease
Published on: June 17, 2013
Multimodal MRI Evaluation of the MitoPark Mouse Model of Parkinson's Disease
Linlin Cong1,2, Eric R Muir1,3, Cang Chen4
1Research Imaging Institute, University of Texas Health Science Center, San Antonio, Texas, United States of America.
Abstract:
The MitoPark mouse, a relatively new genetic model of Parkinson's disease (PD), has a dopaminergic neuron-specific knock-out that inactivates the mitochondrial transcription factor A (Tfam), a protein essential for mitochondrial DNA expression and maintenance. This study used multimodal MRI to characterize the neuroanatomical correlates of PD-related deficits in MitoPark mice, along with functional behavioral tests. Compared with age-matched wild-type animals, MitoPark mice at 30 weeks showed: i) reduced whole-brain volume and increased ventricular volume, indicative of brain atrophy, ii) reduced transverse relaxation time (T2*) of the substantia nigra and striatum, suggestive of abnormal iron accumulation, iii) reduced apparent diffusion coefficient in the substantia nigra, suggestive of neuronal loss, iv) reduced fractional anisotropy in the corpus callosum and substantia nigra, indicative of white-matter damages, v) cerebral blood flow was not significantly affected, and vi) reduced motor activity in open-field tests, reduced memory in novel object recognition tests, as well as decreased mobility in tail suspension tests, an indication of depression. In sum, MitoPark mice recapitulate changes in many MRI parameters reported in PD patients. Multimodal MRI may prove useful for evaluating neuroanatomical correlates of PD pathophysiology in MitoPark mice, and for longitudinally monitoring disease progression and therapeutic interventions for PD.
Insights
The MitoPark mouse model of Parkinson's disease (PD) exhibits brain atrophy and white matter damage. Multimodal MRI reveals PD-related neuroanatomical changes and behavioral deficits in these mice.
Area of Science:
- Neuroscience
- Genetics
- Medical Imaging
Background:
- Parkinson's disease (PD) is a neurodegenerative disorder.
- The MitoPark mouse is a genetic model of PD with impaired mitochondrial function.
- Mitochondrial dysfunction is implicated in PD pathogenesis.
Purpose of the Study:
- To characterize neuroanatomical changes in MitoPark mice using multimodal MRI.
- To correlate MRI findings with behavioral deficits in this PD model.
- To assess the utility of MRI for studying PD progression.
Main Methods:
- Multimodal magnetic resonance imaging (MRI) techniques.
- Functional behavioral tests including open-field, novel object recognition, and tail suspension tests.
- Comparison between 30-week-old MitoPark mice and age-matched wild-type controls.
Main Results:
- MitoPark mice showed brain atrophy (reduced whole-brain volume, increased ventricular volume).
- MRI revealed substantia nigra and striatum T2* reduction (iron accumulation) and reduced ADC (neuronal loss).
- White matter integrity was compromised (reduced fractional anisotropy in corpus callosum and substantia nigra), with no significant change in cerebral blood flow. Behavioral tests indicated motor deficits, memory impairment, and depressive-like symptoms.
Conclusions:
- MitoPark mice display significant neuroanatomical and behavioral alterations mirroring human PD.
- Multimodal MRI effectively captures PD-related pathology in the MitoPark model.
- This model and MRI approach are valuable for investigating PD pathophysiology and evaluating therapies.
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