title: Dopaminergic Neurodegeneration in the Mouse Is Associated with Decrease of Viscoelasticity of Substantia Nigra Tissue.
abstract: The biomechanical properties of brain tissue are altered by histopathological changes due to neurodegenerative diseases like Parkinson's disease (PD). Such alterations can be measured by magnetic resonance elastography (MRE) as a non-invasive technique to determine viscoelastic parameters of the brain. Until now, the correlation between histopathological mechanisms and observed alterations in tissue viscoelasticity in neurodegenerative diseases is still not completely understood. Thus, the objective of this study was to evaluate (1) the validity of MRE to detect viscoelastic changes in small and specific brain regions: the substantia nigra (SN), midbrain and hippocampus in a mouse model of PD, and (2) if the induced dopaminergic neurodegeneration and inflammation in the SN is reflected by local changes in viscoelasticity. Therefore, MRE measurements of the SN, midbrain and hippocampus were performed in adult female mice before and at five time points after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridin hydrochloride (MPTP) treatment specifically lesioning dopaminergic neurons in the SN. At each time point, additional mice were utilized for histological analysis of the SN. After treatment cessation, we observed opposed viscoelastic changes in the midbrain, hippocampus and SN with the midbrain showing a gradual rise and the hippocampus a distinct transient increase of viscous and elastic parameters, while viscosity and-to a lesser extent-elasticity in the SN decreased over time. The decrease in viscosity and elasticity in the SN was paralleled by a reduced number of neurons due to the MPTP-induced neurodegeneration. In conclusion, MRE is highly sensitive to detect local viscoelastic changes in specific and even small brain regions. Moreover, we confirmed that neuronal cells likely constitute the backbone of the adult brain mainly accounting for its viscoelasticity. Therefore, MRE could be established as a new potential instrument for clinical evaluation and diagnostics of neurodegenerative diseases.
authors.affiliation: Department of Neurology, Charité, University Medicine Berlin, Berlin, Germany.
authors.forename: Elisabeth G
authors.initials: EG
authors.lastname: Hain
authors.affiliation: Department of Neurology, Charité, University Medicine Berlin, Berlin, Germany.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Klein
authors.affiliation: Department of Neurology, Charité, University Medicine Berlin, Berlin, Germany.
authors.forename: Tonia
authors.initials: T
authors.lastname: Munder
authors.affiliation: Institute for Medical Informatics, Charité, University Medicine Berlin, Berlin, Germany.
authors.forename: Juergen
authors.initials: J
authors.lastname: Braun
authors.affiliation: Department of Radiology, Charité, University Medicine Berlin, Berlin, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Riek
authors.affiliation: Center for Stroke Research Berlin, Berlin, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Mueller
authors.affiliation: Department of Radiology, Charité, University Medicine Berlin, Berlin, Germany.
authors.forename: Ingolf
authors.initials: I
authors.lastname: Sack
authors.affiliation: Department of Neurology, Charité, University Medicine Berlin, Berlin, Germany.
authors.forename: Barbara
authors.initials: B
authors.lastname: Steiner
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology; D000818:Animals; D004298:Dopamine / Q000378:metabolism*; D004548:Elasticity / Q000187:drug effects; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000187:drug effects / Q000473:pathology; D010300:Parkinson Disease / Q000378:metabolism / Q000473:pathology*; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D014783:Viscosity / Q000187:drug effects
chemical_list: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D004298:Dopamine