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

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68081731%3A_____%2F17%3A00477748" target="_blank" >RIV/68081731:_____/17:00477748 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216224:14740/17:00096844

Výsledek na webu

<a href="http://dx.doi.org/10.1016/j.bbi.2016.11.027" target="_blank" >http://dx.doi.org/10.1016/j.bbi.2016.11.027</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.bbi.2016.11.027" target="_blank" >10.1016/j.bbi.2016.11.027</a>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10700 - Other natural sciences

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2017

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Brain Behavior and Immunity

ISSN

0889-1591

e-ISSN

—

Svazek periodika

61

Číslo periodika v rámci svazku

MAR

Stát vydavatele periodika

CA - Kanada

Počet stran výsledku

12

Strana od-do

197-208

Kód UT WoS článku

000395365900022

EID výsledku v databázi Scopus

2-s2.0-85010773884