Early and progressive microstructural brain changes in mice overexpressing human alpha-Synuclein detected by diffusion kurtosis imaging

Warning

This publication doesn't include Faculty of Sports Studies. It includes Central European Institute of Technology. Official publication website can be found on muni.cz.
Authors

KHAIRNAR Amit Suresh RUDÁ Jana SZABÓ Nikoletta DRAŽANOVÁ Eva ARAB Anas HUTTER-PAIER Birgit NEDDENS Joerg LATTA Peter STARČUK Zenon REKTOROVÁ Irena

Year of publication 2017
Type Article in Periodical
Magazine / Source Brain, Behavior, and Immunity
MU Faculty or unit

Central European Institute of Technology

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:

You are running an old browser version. We recommend updating your browser to its latest version.

More info