Diffusion Kurtosis Imaging Detects Microstructural Alterations in Brain of α-Synuclein Overexpressing Transgenic Mouse Model of Parkinson’s Disease: A Pilot Study

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• 作者：Amit Khairnar ; Peter Latta ; Eva Drazanova ; Jana Ruda-Kucerova…
• 关键词：Diffusion kurtosis imaging ; α ; Synuclein ; TNWT ; 61 ; Parkinson’s disease ; Transgenic mice ; TBSS
• 刊名：Neurotoxicity Research
• 出版年：2015
• 出版时间：November 2015
• 年：2015
• 卷：28
• 期：4
• 页码：281-289
• 全文大小：943 KB
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• 作者单位：Amit Khairnar (1) <br> Peter Latta (2) <br> Eva Drazanova (3) (5) <br> Jana Ruda-Kucerova (4) (5) <br> Nikoletta Szabó (6) <br> Anas Arab (4) (5) <br> Birgit Hutter-Paier (7) <br> Daniel Havas (7) <br> Manfred Windisch (8) <br> Alexandra Sulcova (4) <br> Zenon Starcuk Jr. (2) (3) <br> Irena Rektorova (1) <br><br>1. Applied Neuroscience Research Group, CEITEC - Central European Institute of Technology, Masaryk University, Kamenice 5, 625 00, Brno, Czech Republic <br> 2. Multimodal and Functional Imaging Laboratory, CEITEC - Central European Institute of Technology, Masaryk University, Brno, Czech Republic <br> 3. Institute of Scientific Instruments, Academy of Sciences of the Czech Republic, Brno, Czech Republic <br> 5. Department of Pharmacology, Faculty of Medicine, Masaryk University, Brno, Czech Republic <br> 4. Experimental and Applied Neuropsychopharmacology Group, CEITEC - Central European Institute of Technology, Masaryk University, Brno, Czech Republic <br> 6. Department of Neurology, Faculty of Medicine, Albert Szent-Gy?rgyi Clinical Centre, University of Szeged, Szeged, Hungary <br> 7. QPS Austria GmbH, Grambach, Austria <br> 8. NeuroScios GmbH, Graz, Austria <br>
• 刊物主题：Neurosciences; Neurology; Neurochemistry; Pharmacology/Toxicology; Neurobiology; Cell Biology;
• 出版者：Springer US
• ISSN：1476-3524

文摘

Evidence suggests that accumulation and aggregation of α-synuclein contribute to the pathogenesis of Parkinson’s disease (PD). The aim of this study was to evaluate whether diffusion kurtosis imaging (DKI) will provide a sensitive tool for differentiating between α-synuclein-overexpressing transgenic mouse model of PD (TNWT-61) and wild-type (WT) littermates. This experiment was designed as a proof-of-concept study and forms a part of a complex protocol and ongoing translational research. Nine-month-old TNWT-61 mice and age-matched WT littermates underwent behavioral tests to monitor motor impairment and MRI scanning using 9.4 Tesla system in vivo. Tract-based spatial statistics (TBSS) and the DKI protocol were used to compare the whole brain white matter of TNWT-61 and WT mice. In addition, region of interest (ROI) analysis was performed in gray matter regions such as substantia nigra, striatum, hippocampus, sensorimotor cortex, and thalamus known to show higher accumulation of α-synuclein. For the ROI analysis, both DKI (6 b-values) protocol and conventional (2 b-values) diffusion tensor imaging (cDTI) protocol were used. TNWT-61 mice showed significant impairment of motor coordination. With the DKI protocol, mean, axial, and radial kurtosis were found to be significantly elevated, whereas mean and radial diffusivity were decreased in the TNWT-61 group compared to that in the WT controls with both TBSS and ROI analysis. With the cDTI protocol, the ROI analysis showed decrease in all diffusivity parameters in TNWT-61 mice. The current study provides evidence that DKI by providing both kurtosis and diffusivity parameters gives unique information that is complementary to cDTI for in vivo detection of pathological changes that underlie PD-like symptomatology in TNWT-61 mouse model of PD. This result is a crucial step in search for a candidate diagnostic biomarker with translational potential and relevance for human studies. Keywords Diffusion kurtosis imaging α-Synuclein TNWT-61 Parkinson’s disease Transgenic mice TBSS