title: Multimodal MRI Evaluation of the MitoPark Mouse Model of Parkinson's Disease.
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.
authors.affiliation: Research Imaging Institute, University of Texas Health Science Center, San Antonio, Texas, United States of America.|Graduate School of Biomedical Science, University of Texas at San Antonio, San Antonio, Texas, United States of America.
authors.forename: Linlin
authors.initials: L
authors.lastname: Cong
authors.affiliation: Research Imaging Institute, University of Texas Health Science Center, San Antonio, Texas, United States of America.|Department of Ophthalmology, University of Texas Health Science Center, San Antonio, Texas, United States of America.
authors.forename: Eric R
authors.initials: ER
authors.lastname: Muir
authors.affiliation: Department of Medicine, University of Texas Health Science Center, San Antonio, Texas, United States of America.
authors.forename: Cang
authors.initials: C
authors.lastname: Chen
authors.affiliation: Department of Medicine, University of Texas Health Science Center, San Antonio, Texas, United States of America.
authors.forename: Yusheng
authors.initials: Y
authors.lastname: Qian
authors.affiliation: Department of Medicine, University of Texas Health Science Center, San Antonio, Texas, United States of America.
authors.forename: Jingwei
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Medicine, University of Texas Health Science Center, San Antonio, Texas, United States of America.
authors.forename: K C
authors.initials: KC
authors.lastname: Biju
authors.affiliation: Department of Medicine, University of Texas Health Science Center, San Antonio, Texas, United States of America.|South Texas Veterans Health Care System, Department of Veterans Affairs, San Antonio, Texas, United States of America.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Clark
authors.affiliation: Department of Medicine, University of Texas Health Science Center, San Antonio, Texas, United States of America.|South Texas Veterans Health Care System, Department of Veterans Affairs, San Antonio, Texas, United States of America.
authors.forename: Senlin
authors.initials: S
authors.lastname: Li
authors.affiliation: Research Imaging Institute, University of Texas Health Science Center, San Antonio, Texas, United States of America.|Department of Ophthalmology, University of Texas Health Science Center, San Antonio, Texas, United States of America.|South Texas Veterans Health Care System, Department of Veterans Affairs, San Antonio, Texas, United States of America.
authors.forename: Timothy Q
authors.initials: TQ
authors.lastname: Duong
mesh_terms: D000818:Animals; D001284:Atrophy / Q000235:genetics / Q000473:pathology; D001522:Behavior, Animal / Q000502:physiology; D003342:Corpus Striatum / Q000473:pathology*; D004272:DNA, Mitochondrial / Q000096:biosynthesis; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D006609:High Mobility Group Proteins / Q000037:antagonists & inhibitors / Q000235:genetics; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000235:genetics; D064847:Multimodal Imaging / Q000379:methods*; D010300:Parkinson Disease / Q000503:physiopathology*; D013378:Substantia Nigra / Q000473:pathology*; D013737:Testis / Q000502:physiology*
chemical_list: D004272:DNA, Mitochondrial; D004268:DNA-Binding Proteins; D006609:High Mobility Group Proteins; C081930:Tfam protein, mouse