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

J 2017

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

KHAIRNAR, Amit Suresh, Jana RUDÁ, Nikoletta SZABÓ, Eva DRAŽANOVÁ, Anas ARAB et. al.

Basic information

Original name

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

Authors

KHAIRNAR, Amit Suresh (356 India, belonging to the institution), Jana RUDÁ (203 Czech Republic, belonging to the institution), Nikoletta SZABÓ (348 Hungary), Eva DRAŽANOVÁ (203 Czech Republic, belonging to the institution), Anas ARAB (760 Syrian Arab Republic, belonging to the institution), Birgit HUTTER-PAIER (40 Austria), Joerg NEDDENS (40 Austria), Peter LATTA (703 Slovakia, belonging to the institution), Zenon STARČUK (203 Czech Republic, belonging to the institution) and Irena REKTOROVÁ (203 Czech Republic, guarantor, belonging to the institution)

Edition

Brain, Behavior, and Immunity, San Diego, Academic Press, 2017, 0889-1591

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30102 Immunology

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 6.306

RIV identification code

RIV/00216224:14740/17:00096844

Organization unit

Central European Institute of Technology

DOI

http://dx.doi.org/10.1016/j.bbi.2016.11.027

UT WoS

000395365900022

Keywords in English

MRI; Diffusion kurtosis imaging; Substantia nigra; Striatum; Thalamus; TNWT-61; Parkinson's disease; Transgenic mice; Animal model

Abstract

V originále

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.

Links

LM2015062, research and development project

Name: Národní infrastruktura pro biologické a medicínské zobrazování

Investor: Ministry of Education, Youth and Sports of the CR

LQ1601, research and development project

Name: CEITEC 2020 (Acronym: CEITEC2020)

Investor: Ministry of Education, Youth and Sports of the CR

MUNI/A/1063/2016, interní kód MU

Name: Experimentální a translační farmakologický výzkum a vývoj

Investor: Masaryk University, Category A

Citovat

KHAIRNAR, Amit Suresh, Jana RUDÁ, Nikoletta SZABÓ, Eva DRAŽANOVÁ, Anas ARAB, Birgit HUTTER-PAIER, Joerg NEDDENS, Peter LATTA, Zenon STARČUK and Irena REKTOROVÁ. Early and progressive microstructural brain changes in mice overexpressing human alpha-Synuclein detected by diffusion kurtosis imaging. Brain, Behavior, and Immunity. San Diego: Academic Press, 2017, vol. 61, March, p. 197-208. ISSN 0889-1591. Available from: https://dx.doi.org/10.1016/j.bbi.2016.11.027.

@article{1381942,
   author = {Khairnar, Amit Suresh and Rudá, Jana and Szabó, Nikoletta and Dražanová, Eva and Arab, Anas and HutterandPaier, Birgit and Neddens, Joerg and Latta, Peter and Starčuk, Zenon and Rektorová, Irena},
   article_location = {San Diego},
   article_number = {March},
   doi = {http://dx.doi.org/10.1016/j.bbi.2016.11.027},
   keywords = {MRI; Diffusion kurtosis imaging; Substantia nigra; Striatum; Thalamus; TNWT-61; Parkinson's disease; Transgenic mice; Animal model},
   language = {eng},
   issn = {0889-1591},
   journal = {Brain, Behavior, and Immunity},
   title = {Early and progressive microstructural brain changes in mice overexpressing human alpha-Synuclein detected by diffusion kurtosis imaging},
   url = {http://www.sciencedirect.com/science/article/pii/S0889159116305293},
   volume = {61},
   year = {2017}
}

TY  - JOUR
ID  - 1381942
AU  - Khairnar, Amit Suresh - Rudá, Jana - Szabó, Nikoletta - Dražanová, Eva - Arab, Anas - Hutter-Paier, Birgit - Neddens, Joerg - Latta, Peter - Starčuk, Zenon - Rektorová, Irena
PY  - 2017
TI  - Early and progressive microstructural brain changes in mice overexpressing human alpha-Synuclein detected by diffusion kurtosis imaging
JF  - Brain, Behavior, and Immunity
VL  - 61
IS  - March
SP  - 197-208
EP  - 197-208
PB  - Academic Press
SN  - 08891591
KW  - MRI
KW  - Diffusion kurtosis imaging
KW  - Substantia nigra
KW  - Striatum
KW  - Thalamus
KW  - TNWT-61
KW  - Parkinson's disease
KW  - Transgenic mice
KW  - Animal model
UR  - http://www.sciencedirect.com/science/article/pii/S0889159116305293
L2  - http://www.sciencedirect.com/science/article/pii/S0889159116305293
N2  - 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.
ER  -

KHAIRNAR, Amit Suresh, Jana RUDÁ, Nikoletta SZABÓ, Eva DRAŽANOVÁ, Anas ARAB, Birgit HUTTER-PAIER, Joerg NEDDENS, Peter LATTA, Zenon STARČUK and Irena REKTOROVÁ. Early and progressive microstructural brain changes in mice overexpressing human alpha-Synuclein detected by diffusion kurtosis imaging. \textit{Brain, Behavior, and Immunity}. San Diego: Academic Press, 2017, vol.~61, March, p.~197-208. ISSN~0889-1591. Available from: https://dx.doi.org/10.1016/j.bbi.2016.11.027.

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