title: Assessment of brain metabolite correlates of adeno-associated virus-mediated over-expression of human alpha-synuclein in cortical neurons by in vivo (1) H-MR spectroscopy at 9.4 T.
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 (α-syn) over-expression. Our goal was to find out if the increased α-syn load in this model could be linked to changes in metabolites in the frontal cortex. Animals injected with AAV vectors encoding for human α-syn formed the experimental group, whereas green fluorescent protein expressing animals were used as the vector-treated control group and a third group of uninjected animals were used as naïve controls. Data were acquired at 2, 4, and 8 month time points. Nineteen metabolites were quantified in the MR spectra using LCModel software. On the basis of 92 spectra, we evaluated any potential gender effect and found that lactate (Lac) levels were lower in males compared to females, while the opposite was observed for ascorbate (Asc). 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 Lac levels (p = 0.005) were specifically lower in the α-syn group compared to the green fluorescent protein and control groups. In addition, Asc levels (p = 0.05) were increased in the vector-injected groups, whereas glucose levels remained unchanged. This study indicates that the metabolic switch between glucose-lactate could be detectable in vivo and might be modulated by Asc. No concomitant changes were found in markers of neuronal integrity (e.g., N-acetylaspartate) consistent with the fact that α-syn over-expression in cortical neurons did not result in neurodegeneration in this model. We acquired the neurochemical profile longitudinally in a rat model of human wild-type alpha-synuclein (α-syn) over-expression in cortical neurons. We found that Lactate levels were reduced in the α-syn group compared to the control groups and Ascorbate levels were increased in the vector-injected groups. No changes were found in markers of neuronal integrity consistent with the fact that α-syn over-expression did not result in frank neurodegeneration.
authors.affiliation: Brain Repair And Imaging in Neural Systems (B.R.A.I.N.S), Department of Experimental Medical Science, Lund University, Lund, Sweden.
authors.forename: Sandra
authors.initials: S
authors.lastname: Cuellar-Baena
authors.affiliation: Brain Repair And Imaging in Neural Systems (B.R.A.I.N.S), Department of Experimental Medical Science, Lund University, Lund, Sweden.
authors.forename: Natalie
authors.initials: N
authors.lastname: Landeck
authors.affiliation: Brain Repair And Imaging in Neural Systems (B.R.A.I.N.S), Department of Experimental Medical Science, Lund University, Lund, Sweden.|Laboratory of functional and metabolic imaging (LIFMET), École Polytechnique Fédérale de Lausanne EPFL, Lausanne, Switzerland.
authors.forename: Sarah
authors.initials: S
authors.lastname: Sonnay
authors.affiliation: Brain Repair And Imaging in Neural Systems (B.R.A.I.N.S), Department of Experimental Medical Science, Lund University, Lund, Sweden.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Buck
authors.affiliation: Laboratory of functional and metabolic imaging (LIFMET), École Polytechnique Fédérale de Lausanne EPFL, Lausanne, Switzerland.|Department of Radiology and Nuclear Medicine, Medical University of Vienna, Vienna, Austria.
authors.forename: Vladimir
authors.identifier: 0000-0002-5789-8179
authors.initials: V
authors.lastname: Mlynarik
authors.affiliation: Lund University BioImaging Center, Lund University, Lund, Sweden.
authors.forename: René
authors.initials: R
authors.lastname: In 't Zandt
authors.affiliation: Brain Repair And Imaging in Neural Systems (B.R.A.I.N.S), Department of Experimental Medical Science, Lund University, Lund, Sweden.|Lund University BioImaging Center, Lund University, Lund, Sweden.
authors.forename: Deniz
authors.initials: D
authors.lastname: Kirik
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism*; D000229:Dependovirus; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D006859:Hydrogen; D008137:Longitudinal Studies; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008297:Male; D009474:Neurons / Q000378:metabolism*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D051844:alpha-Synuclein / Q000096:biosynthesis*
chemical_list: D051844:alpha-Synuclein; D006859:Hydrogen
keywords: adeno-associated virus; alpha-synuclein; lactate-glucose-ascorbate shuttle; linear mixed-model; proton magnetic resonance spectroscopy