title: Early and progressive microstructural brain changes in mice overexpressing human α-Synuclein detected by diffusion kurtosis imaging.
abstract: Diffusion kurtosis imaging (DKI) is sensitive in detecting α-Synuclein (α-Syn) accumulation-associated microstructural changes at late stages of the pathology in α-Syn overexpressing TNWT-61 mice. The aim of this study was to perform DKI in young TNWT-61 mice when α-Syn starts to accumulate and to compare the imaging results with an analysis of motor and memory impairment and α-Syn levels. Three-month-old (3mo) and six-month-old (6mo) mice underwent DKI scanning using the Bruker Avance 9.4T magnetic resonance imaging system. Region of interest (ROI) analyses were performed in the gray matter; tract-based spatial statistics (TBSS) analyses were performed in the white matter. In the same mice, α-Syn expression was evaluated using quantitative immunofluorescence. Mean kurtosis (MK) was the best differentiator between TNWT-61 mice and wildtype (WT) mice. We found increases in MK in 3mo TNWT-61 mice in the striatum and thalamus but not in the substantia nigra (SN), hippocampus, or sensorimotor cortex, even though the immunoreactivity of human α-Syn was similar or even higher in the latter regions. Increases in MK in the SN were detected in 6mo mice. These findings indicate that α-Syn accumulation-associated changes may start in areas with a high density of dopaminergic nerve terminals. We also found TBSS changes in white matter only at 6mo, suggesting α-Syn accumulation-associated changes start in the gray matter and later progress to the white matter. MK is able to detect microstructural changes induced by α-Syn overexpression in TNWT-61 mice and could be a useful clinical tool for detecting early-stage Parkinson's disease in human patients.
authors.affiliation: Applied Neuroscience Research Group, CEITEC - Central European Institute of Technology, Masaryk University, Brno, Czech Republic.
authors.forename: Amit
authors.initials: A
authors.lastname: Khairnar
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Masaryk University, Brno, Czech Republic.
authors.forename: Jana
authors.initials: J
authors.lastname: Ruda-Kucerova
authors.affiliation: Department of Neurology, Faculty of Medicine, Albert Szent-Györgyi Clinical Centre, University of Szeged, Szeged, Hungary.
authors.forename: Nikoletta
authors.initials: N
authors.lastname: Szabó
authors.affiliation: Institute of Scientific Instruments, Academy of Sciences of the Czech Republic, Brno, Czech Republic; Department of Pharmacology, Faculty of Medicine, Masaryk University, Brno, Czech Republic.
authors.forename: Eva
authors.initials: E
authors.lastname: Drazanova
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Masaryk University, Brno, Czech Republic.
authors.forename: Anas
authors.initials: A
authors.lastname: Arab
authors.affiliation: QPS Austria GmbH, Grambach, Austria.
authors.forename: Birgit
authors.initials: B
authors.lastname: Hutter-Paier
authors.affiliation: QPS Austria GmbH, Grambach, Austria.
authors.forename: Joerg
authors.initials: J
authors.lastname: Neddens
authors.affiliation: Multimodal and Functional Imaging Laboratory, CEITEC - Central European Institute of Technology, Masaryk University, Brno, Czech Republic.
authors.forename: Peter
authors.initials: P
authors.lastname: Latta
authors.affiliation: Institute of Scientific Instruments, Academy of Sciences of the Czech Republic, Brno, Czech Republic; Multimodal and Functional Imaging Laboratory, CEITEC - Central European Institute of Technology, Masaryk University, Brno, Czech Republic.
authors.forename: Zenon
authors.initials: Z
authors.lastname: Starcuk
authors.affiliation: Applied Neuroscience Research Group, CEITEC - Central European Institute of Technology, Masaryk University, Brno, Czech Republic. Electronic address: irena.rektorova@ceitec.muni.cz.
authors.forename: Irena
authors.initials: I
authors.lastname: Rektorova
mesh_terms: D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism; D038524:Diffusion Magnetic Resonance Imaging; D004195:Disease Models, Animal; D008568:Memory / Q000502:physiology*; D051379:Mice; D009043:Motor Activity / Q000502:physiology; D009048:Motor Skills / Q000502:physiology; D010300:Parkinson Disease / Q000000981:diagnostic imaging* / Q000235:genetics / Q000378:metabolism; D051844:alpha-Synuclein / Q000235:genetics* / Q000378:metabolism
chemical_list: C497605:Snca protein, mouse; D051844:alpha-Synuclein
keywords: Animal model; Diffusion kurtosis imaging; MRI; Parkinson’s disease; Striatum; Substantia nigra; TNWT-61; Thalamus; Transgenic mice