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.
Highlights
Parkinson's disease (PD) the second most common neurodegenerative disease, is characterized primarily by death of dopaminergic (DA) neurons in the substantia nigra [1]
Respiration rate (113–150 bpm), heart rate (403–580 bpm) and arterial oxygen saturation (93%-99%) of all animals were within normal physiological ranges and there were no significant differences in these physiological parameters between the two animal groups (p > 0.05)
The whole-brain volume of MitoPark mice (262±12 mm3) was smaller by 10% compared with wild-type mice (292±10 mm3, p < 0.001), suggesting brain tissue atrophy
Summary
Parkinson's disease (PD) the second most common neurodegenerative disease, is characterized primarily by death of dopaminergic (DA) neurons in the substantia nigra [1]. The specific etiology of PD remains unknown. Current PD treatments are primarily based on pharmacological replacement of dopamine to treat motor symptoms, providing only symptomatic relief for a few years in the early stages of PD [2]. Animal models provide an important means to investigate PD etiology, pathology, and therapeutic approaches. They include acute toxin models, PLOS ONE | DOI:10.1371/journal.pone.0151884. They include acute toxin models, PLOS ONE | DOI:10.1371/journal.pone.0151884 March 22, 2016
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