Association of exposure to manganese and iron with striatal and thalamic GABA and other neurometabolites - Neuroimaging results from the WELDOX II study

Swaantje Casjens, Urike Dydak, Shalmali Dharmadhikari, Anne Lotz, Martin Lehnert, Clara Quetscher, Christoph Stewig, Benjamin Glaubitz, Tobias Schmidt-Wilcke, David Edmondson, Chien Lin Yeh, Tobias Weiss, Christoph van Thriel, Lennard Herrmann, Siegfried Muhlack, Dirk Woitalla, Michael Aschner, Thomas Brüning, Beate Pesch

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Objective: Magnetic resonance spectroscopy (MRS) is a non-invasive method to quantify neurometabolite concentrations in the brain. Within the framework of the WELDOX II study, we investigated the association of exposure to manganese (Mn) and iron (Fe) with γ-aminobutyric acid (GABA) and other neurometabolites in the striatum and thalamus of 154 men. Material and methods: GABA-edited and short echo-time MRS at 3T was used to assess brain levels of GABA, glutamate, total creatine (tCr) and other neurometabolites. Volumes of interest (VOIs) were placed into the striatum and thalamus of both hemispheres of 47 active welders, 20 former welders, 36 men with Parkinson's disease (PD), 12 men with hemochromatosis (HC), and 39 male controls. Linear mixed models were used to estimate the influence of Mn and Fe exposure on neurometabolites while simultaneously adjusting for cerebrospinal fluid (CSF) content, age and other factors. Exposure to Mn and Fe was assessed by study group, blood concentrations, relaxation rates R1 and R2* in the globus pallidus (GP), and airborne exposure (active welders only). Results: The median shift exposure to respirable Mn and Fe in active welders was 23μg/m3 and 110μg/m3, respectively. Airborne exposure was not associated with any other neurometabolite concentration. Mn in blood and serum ferritin were highest in active and former welders. GABA concentrations were not associated with any measure of exposure to Mn or Fe. In comparison to controls, tCr in these VOIs was lower in welders and patients with PD or HC. Serum concentrations of ferritin and Fe were associated with N-acetylaspartate, but in opposed directions. Higher R1 values in the GP correlated with lower neurometabolite concentrations, in particular tCr (exp(β)=0.87, p<0.01) and choline (exp(β)=0.84, p=0.04). R2* was positively associated with glutamate-glutamine and negatively with myo-inositol. Conclusions: Our results do not provide evidence that striatal and thalamic GABA differ between Mn-exposed workers, PD or HC patients, and controls. This may be due to the low exposure levels of the Mn-exposed workers and the challenges to detect small changes in GABA. Whereas Mn in blood was not associated with any neurometabolite content in these VOIs, a higher metal accumulation in the GP assessed with R1 correlated with generally lower neurometabolite concentrations.

Original languageEnglish (US)
JournalNeuroToxicology
DOIs
StateAccepted/In press - 2017

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Neuroimaging
Corpus Striatum
Manganese
gamma-Aminobutyric Acid
Iron
Globus Pallidus
Hemochromatosis
Creatine
Magnetic resonance spectroscopy
Ferritins
Thalamus
Parkinson Disease
Glutamic Acid
Brain
Blood
Magnetic Resonance Spectroscopy
Cerebrospinal fluid
Aminobutyrates
Age Factors
Inositol

Keywords

  • Globus pallidus
  • Glutamate
  • Haemochromatosis
  • Magnetic resonance spectroscopy
  • Parkinson
  • Welders

ASJC Scopus subject areas

  • Neuroscience(all)
  • Toxicology

Cite this

Association of exposure to manganese and iron with striatal and thalamic GABA and other neurometabolites - Neuroimaging results from the WELDOX II study. / Casjens, Swaantje; Dydak, Urike; Dharmadhikari, Shalmali; Lotz, Anne; Lehnert, Martin; Quetscher, Clara; Stewig, Christoph; Glaubitz, Benjamin; Schmidt-Wilcke, Tobias; Edmondson, David; Yeh, Chien Lin; Weiss, Tobias; Thriel, Christoph van; Herrmann, Lennard; Muhlack, Siegfried; Woitalla, Dirk; Aschner, Michael; Brüning, Thomas; Pesch, Beate.

In: NeuroToxicology, 2017.

Research output: Contribution to journalArticle

Casjens, S, Dydak, U, Dharmadhikari, S, Lotz, A, Lehnert, M, Quetscher, C, Stewig, C, Glaubitz, B, Schmidt-Wilcke, T, Edmondson, D, Yeh, CL, Weiss, T, Thriel, CV, Herrmann, L, Muhlack, S, Woitalla, D, Aschner, M, Brüning, T & Pesch, B 2017, 'Association of exposure to manganese and iron with striatal and thalamic GABA and other neurometabolites - Neuroimaging results from the WELDOX II study', NeuroToxicology. https://doi.org/10.1016/j.neuro.2017.08.004
Casjens, Swaantje ; Dydak, Urike ; Dharmadhikari, Shalmali ; Lotz, Anne ; Lehnert, Martin ; Quetscher, Clara ; Stewig, Christoph ; Glaubitz, Benjamin ; Schmidt-Wilcke, Tobias ; Edmondson, David ; Yeh, Chien Lin ; Weiss, Tobias ; Thriel, Christoph van ; Herrmann, Lennard ; Muhlack, Siegfried ; Woitalla, Dirk ; Aschner, Michael ; Brüning, Thomas ; Pesch, Beate. / Association of exposure to manganese and iron with striatal and thalamic GABA and other neurometabolites - Neuroimaging results from the WELDOX II study. In: NeuroToxicology. 2017.
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abstract = "Objective: Magnetic resonance spectroscopy (MRS) is a non-invasive method to quantify neurometabolite concentrations in the brain. Within the framework of the WELDOX II study, we investigated the association of exposure to manganese (Mn) and iron (Fe) with γ-aminobutyric acid (GABA) and other neurometabolites in the striatum and thalamus of 154 men. Material and methods: GABA-edited and short echo-time MRS at 3T was used to assess brain levels of GABA, glutamate, total creatine (tCr) and other neurometabolites. Volumes of interest (VOIs) were placed into the striatum and thalamus of both hemispheres of 47 active welders, 20 former welders, 36 men with Parkinson's disease (PD), 12 men with hemochromatosis (HC), and 39 male controls. Linear mixed models were used to estimate the influence of Mn and Fe exposure on neurometabolites while simultaneously adjusting for cerebrospinal fluid (CSF) content, age and other factors. Exposure to Mn and Fe was assessed by study group, blood concentrations, relaxation rates R1 and R2* in the globus pallidus (GP), and airborne exposure (active welders only). Results: The median shift exposure to respirable Mn and Fe in active welders was 23μg/m3 and 110μg/m3, respectively. Airborne exposure was not associated with any other neurometabolite concentration. Mn in blood and serum ferritin were highest in active and former welders. GABA concentrations were not associated with any measure of exposure to Mn or Fe. In comparison to controls, tCr in these VOIs was lower in welders and patients with PD or HC. Serum concentrations of ferritin and Fe were associated with N-acetylaspartate, but in opposed directions. Higher R1 values in the GP correlated with lower neurometabolite concentrations, in particular tCr (exp(β)=0.87, p<0.01) and choline (exp(β)=0.84, p=0.04). R2* was positively associated with glutamate-glutamine and negatively with myo-inositol. Conclusions: Our results do not provide evidence that striatal and thalamic GABA differ between Mn-exposed workers, PD or HC patients, and controls. This may be due to the low exposure levels of the Mn-exposed workers and the challenges to detect small changes in GABA. Whereas Mn in blood was not associated with any neurometabolite content in these VOIs, a higher metal accumulation in the GP assessed with R1 correlated with generally lower neurometabolite concentrations.",
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year = "2017",
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TY - JOUR

T1 - Association of exposure to manganese and iron with striatal and thalamic GABA and other neurometabolites - Neuroimaging results from the WELDOX II study

AU - Casjens, Swaantje

AU - Dydak, Urike

AU - Dharmadhikari, Shalmali

AU - Lotz, Anne

AU - Lehnert, Martin

AU - Quetscher, Clara

AU - Stewig, Christoph

AU - Glaubitz, Benjamin

AU - Schmidt-Wilcke, Tobias

AU - Edmondson, David

AU - Yeh, Chien Lin

AU - Weiss, Tobias

AU - Thriel, Christoph van

AU - Herrmann, Lennard

AU - Muhlack, Siegfried

AU - Woitalla, Dirk

AU - Aschner, Michael

AU - Brüning, Thomas

AU - Pesch, Beate

PY - 2017

Y1 - 2017

N2 - Objective: Magnetic resonance spectroscopy (MRS) is a non-invasive method to quantify neurometabolite concentrations in the brain. Within the framework of the WELDOX II study, we investigated the association of exposure to manganese (Mn) and iron (Fe) with γ-aminobutyric acid (GABA) and other neurometabolites in the striatum and thalamus of 154 men. Material and methods: GABA-edited and short echo-time MRS at 3T was used to assess brain levels of GABA, glutamate, total creatine (tCr) and other neurometabolites. Volumes of interest (VOIs) were placed into the striatum and thalamus of both hemispheres of 47 active welders, 20 former welders, 36 men with Parkinson's disease (PD), 12 men with hemochromatosis (HC), and 39 male controls. Linear mixed models were used to estimate the influence of Mn and Fe exposure on neurometabolites while simultaneously adjusting for cerebrospinal fluid (CSF) content, age and other factors. Exposure to Mn and Fe was assessed by study group, blood concentrations, relaxation rates R1 and R2* in the globus pallidus (GP), and airborne exposure (active welders only). Results: The median shift exposure to respirable Mn and Fe in active welders was 23μg/m3 and 110μg/m3, respectively. Airborne exposure was not associated with any other neurometabolite concentration. Mn in blood and serum ferritin were highest in active and former welders. GABA concentrations were not associated with any measure of exposure to Mn or Fe. In comparison to controls, tCr in these VOIs was lower in welders and patients with PD or HC. Serum concentrations of ferritin and Fe were associated with N-acetylaspartate, but in opposed directions. Higher R1 values in the GP correlated with lower neurometabolite concentrations, in particular tCr (exp(β)=0.87, p<0.01) and choline (exp(β)=0.84, p=0.04). R2* was positively associated with glutamate-glutamine and negatively with myo-inositol. Conclusions: Our results do not provide evidence that striatal and thalamic GABA differ between Mn-exposed workers, PD or HC patients, and controls. This may be due to the low exposure levels of the Mn-exposed workers and the challenges to detect small changes in GABA. Whereas Mn in blood was not associated with any neurometabolite content in these VOIs, a higher metal accumulation in the GP assessed with R1 correlated with generally lower neurometabolite concentrations.

AB - Objective: Magnetic resonance spectroscopy (MRS) is a non-invasive method to quantify neurometabolite concentrations in the brain. Within the framework of the WELDOX II study, we investigated the association of exposure to manganese (Mn) and iron (Fe) with γ-aminobutyric acid (GABA) and other neurometabolites in the striatum and thalamus of 154 men. Material and methods: GABA-edited and short echo-time MRS at 3T was used to assess brain levels of GABA, glutamate, total creatine (tCr) and other neurometabolites. Volumes of interest (VOIs) were placed into the striatum and thalamus of both hemispheres of 47 active welders, 20 former welders, 36 men with Parkinson's disease (PD), 12 men with hemochromatosis (HC), and 39 male controls. Linear mixed models were used to estimate the influence of Mn and Fe exposure on neurometabolites while simultaneously adjusting for cerebrospinal fluid (CSF) content, age and other factors. Exposure to Mn and Fe was assessed by study group, blood concentrations, relaxation rates R1 and R2* in the globus pallidus (GP), and airborne exposure (active welders only). Results: The median shift exposure to respirable Mn and Fe in active welders was 23μg/m3 and 110μg/m3, respectively. Airborne exposure was not associated with any other neurometabolite concentration. Mn in blood and serum ferritin were highest in active and former welders. GABA concentrations were not associated with any measure of exposure to Mn or Fe. In comparison to controls, tCr in these VOIs was lower in welders and patients with PD or HC. Serum concentrations of ferritin and Fe were associated with N-acetylaspartate, but in opposed directions. Higher R1 values in the GP correlated with lower neurometabolite concentrations, in particular tCr (exp(β)=0.87, p<0.01) and choline (exp(β)=0.84, p=0.04). R2* was positively associated with glutamate-glutamine and negatively with myo-inositol. Conclusions: Our results do not provide evidence that striatal and thalamic GABA differ between Mn-exposed workers, PD or HC patients, and controls. This may be due to the low exposure levels of the Mn-exposed workers and the challenges to detect small changes in GABA. Whereas Mn in blood was not associated with any neurometabolite content in these VOIs, a higher metal accumulation in the GP assessed with R1 correlated with generally lower neurometabolite concentrations.

KW - Globus pallidus

KW - Glutamate

KW - Haemochromatosis

KW - Magnetic resonance spectroscopy

KW - Parkinson

KW - Welders

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