Early and progressive microstructural brain changes in mice overexpressing human alpha-Synuclein detected by diffusion kurtosis imaging
| Authors | |
|---|---|
| Year of publication | 2017 |
| Type | Article in Periodical |
| Magazine / Source | Brain, Behavior, and Immunity |
| MU Faculty or unit | |
| Citation | |
| Web | http://www.sciencedirect.com/science/article/pii/S0889159116305293 |
| Doi | http://dx.doi.org/10.1016/j.bbi.2016.11.027 |
| Field | Immunology |
| Keywords | MRI; Diffusion kurtosis imaging; Substantia nigra; Striatum; Thalamus; TNWT-61; Parkinson's disease; Transgenic mice; Animal model |
| Description | Diffusion kurtosis imaging (DKI) is sensitive in detecting alpha-Synuclein (alpha-Syn) accumulation-associated microstructural changes at late stages of the pathology in alpha-Syn overexpressing TNWT-61 mice. The aim of this study was to perform DKI in young TNWT-61 mice when alpha-Syn starts to accumulate and to compare the imaging results with an analysis of motor and memory impairment and alpha-Syn levels. Three-month-old (3mo) and six-month-old (6mo) mice underwent DIU scanning using the Bruker Avance 9.4 T 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, alpha-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 alpha-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 alpha-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 alpha-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 alpha-Syn overexpression in TNWT-61 mice and could be a useful clinical tool for detecting early-stage Parkinson's disease in human patients. (C) 2016 Elsevier Inc. All rights reserved. |
| Related projects: |