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

0477748 - ÚPT 2018 RIV CA eng J - Článek v odborném periodiku
Khairnar, A. - Rudá-Kučerová, J. - Szabó, N. - Dražanová, Eva - Arab, A. - Hutter-Paier, B. - Neddens, J. - Latta, P. - Starčuk jr., Zenon - Rektorová, I.
Early and progressive microstructural brain changes in mice overexpressing human alpha-Synuclein detected by diffusion kurtosis imaging.
Brain Behavior and Immunity. Roč. 61, MAR (2017), s. 197-208. ISSN 0889-1591. E-ISSN 1090-2139
Grant CEP: GA MŠMT(CZ) LO1212; GA MŠMT(CZ) LM2015062; GA MŠMT ED0017/01/01
Institucionální podpora: RVO:68081731
Klíčová slova: MRI * diffusion kurtosis imaging * substantia nigra * sriatum * thalamus * TNWT-61 * parkinson's disease * transgenic mice * animal model
Obor OECD: 1.7 Other natural sciences
Impakt faktor: 6.306, rok: 2017

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.
Trvalý link: http://hdl.handle.net/11104/0273988