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Assessment of brain metabolite correlates of AAV-mediated overexpression of human alpha-synuclein in cortical neurons by in vivo(1) H-MR spectroscopy at 9.4 T.

Cuellar-Baena, Sandra LU ; Landeck, Natalie LU ; Sonnay, Sarah LU ; Buck, Kerstin LU ; Mlynarik, Vladimir; in 't Zandt, René LU and Kirik, Deniz LU (2016) In Journal of Neurochemistry 137(5). p.806-819
Abstract
In this study, we used proton-localized spectroscopy ((1) H-MRS) for the acquisition of the neurochemical profile longitudinally in a novel rat model of human wild type alpha-synuclein (a-syn) overexpression. Our goal was to find out if the increased a-syn load in this model could be linked to changes in metabolites in the frontal cortex. Animals injected with AAV vectors encoding for human a-syn formed the experimental group, whereas green fluorescent protein (GFP) expressing animals were used as the vector-treated control group and a third group of uninjected animals were used as naïve controls. Data was acquired at 2, 4 and 8 month time-points. Nineteen metabolites were quantified in the MR spectra using LCModel software. Based on 92... (More)
In this study, we used proton-localized spectroscopy ((1) H-MRS) for the acquisition of the neurochemical profile longitudinally in a novel rat model of human wild type alpha-synuclein (a-syn) overexpression. Our goal was to find out if the increased a-syn load in this model could be linked to changes in metabolites in the frontal cortex. Animals injected with AAV vectors encoding for human a-syn formed the experimental group, whereas green fluorescent protein (GFP) expressing animals were used as the vector-treated control group and a third group of uninjected animals were used as naïve controls. Data was acquired at 2, 4 and 8 month time-points. Nineteen metabolites were quantified in the MR spectra using LCModel software. Based on 92 spectra, we evaluated any potential gender effect and found that Lactate levels were lower in males compared to females, while the opposite was observed for Ascorbate. Next, we assessed the effect of age and found increased levels of GABA, Tau and GPC+PCho. Finally, we analyzed the effect of treatment and found that Lactate levels (p=0.005) were specifically lower in the a-syn group compared to the GFP and control groups. Additionally, Ascorbate levels (p=0.05) were increased in the vector-injected groups, while glucose levels remained unchanged. This study indicates that the metabolic switch between Glucose-Lactate could be detectable in-vivo and might be modulated by Ascorbate. No concomitant changes were found in markers of neuronal integrity (e.g. NAA) consistent with the fact that a-syn overexpression in cortical neurons did not result in neurodegeneration in this model. This article is protected by copyright. All rights reserved. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Neurochemistry
volume
137
issue
5
pages
806 - 819
publisher
Wiley-Blackwell
external identifiers
  • pmid:26811128
  • scopus:84959020081
  • wos:000380260600012
ISSN
1471-4159
DOI
10.1111/jnc.13547
language
English
LU publication?
yes
id
9e0bde90-4f5e-4224-8d84-581b216c42be (old id 8573660)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/26811128?dopt=Abstract
date added to LUP
2016-02-04 21:32:21
date last changed
2017-04-20 09:05:25
@article{9e0bde90-4f5e-4224-8d84-581b216c42be,
  abstract     = {In this study, we used proton-localized spectroscopy ((1) H-MRS) for the acquisition of the neurochemical profile longitudinally in a novel rat model of human wild type alpha-synuclein (a-syn) overexpression. Our goal was to find out if the increased a-syn load in this model could be linked to changes in metabolites in the frontal cortex. Animals injected with AAV vectors encoding for human a-syn formed the experimental group, whereas green fluorescent protein (GFP) expressing animals were used as the vector-treated control group and a third group of uninjected animals were used as naïve controls. Data was acquired at 2, 4 and 8 month time-points. Nineteen metabolites were quantified in the MR spectra using LCModel software. Based on 92 spectra, we evaluated any potential gender effect and found that Lactate levels were lower in males compared to females, while the opposite was observed for Ascorbate. Next, we assessed the effect of age and found increased levels of GABA, Tau and GPC+PCho. Finally, we analyzed the effect of treatment and found that Lactate levels (p=0.005) were specifically lower in the a-syn group compared to the GFP and control groups. Additionally, Ascorbate levels (p=0.05) were increased in the vector-injected groups, while glucose levels remained unchanged. This study indicates that the metabolic switch between Glucose-Lactate could be detectable in-vivo and might be modulated by Ascorbate. No concomitant changes were found in markers of neuronal integrity (e.g. NAA) consistent with the fact that a-syn overexpression in cortical neurons did not result in neurodegeneration in this model. This article is protected by copyright. All rights reserved.},
  author       = {Cuellar-Baena, Sandra and Landeck, Natalie and Sonnay, Sarah and Buck, Kerstin and Mlynarik, Vladimir and in 't Zandt, René and Kirik, Deniz},
  issn         = {1471-4159},
  language     = {eng},
  month        = {01},
  number       = {5},
  pages        = {806--819},
  publisher    = {Wiley-Blackwell},
  series       = {Journal of Neurochemistry},
  title        = {Assessment of brain metabolite correlates of AAV-mediated overexpression of human alpha-synuclein in cortical neurons by in vivo(1) H-MR spectroscopy at 9.4 T.},
  url          = {http://dx.doi.org/10.1111/jnc.13547},
  volume       = {137},
  year         = {2016},
}