Early and progressive microstructural brain changes in mice overexpressing human α-Synuclein detected by diffusion kurtosis imaging
Language English Country Netherlands Media print-electronic
Document type Journal Article
PubMed
27923670
DOI
10.1016/j.bbi.2016.11.027
PII: S0889-1591(16)30529-3
Knihovny.cz E-resources
- Keywords
- Animal model, Diffusion kurtosis imaging, MRI, Parkinson’s disease, Striatum, Substantia nigra, TNWT-61, Thalamus, Transgenic mice,
- MeSH
- alpha-Synuclein genetics metabolism MeSH
- Diffusion Magnetic Resonance Imaging * MeSH
- Disease Models, Animal MeSH
- Motor Skills physiology MeSH
- Brain diagnostic imaging metabolism MeSH
- Mice MeSH
- Memory physiology MeSH
- Parkinson Disease diagnostic imaging genetics metabolism MeSH
- Motor Activity physiology MeSH
- Animals MeSH
- Check Tag
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- alpha-Synuclein MeSH
- Snca protein, mouse MeSH Browser
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.
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