In vivo measurement of brain GABA concentrations by magnetic resonance spectroscopy in smelters occupationally exposed to manganese

Ulrike Dydak, Yue Ming Jiang, Li Ling Long, He Zhu, Jian Chen, Wen Mei Li, Richard A E Edden, Shuguang Hu, Xue Fu, Zaiyang Long, Xue An Mo, Dieter Meier, Jaroslaw Harezlak, Michael Aschner, James B. Murdoch, Wei Zheng

Research output: Contribution to journalArticle

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Abstract

Background: Exposure to excessive levels of manganese (Mn) is known to induce psychiatric and motor disorders, including parkinsonian symptoms. Therefore, finding a reliable means for early detection of Mn neurotoxicity is desirable. Objectives: Our goal was to determine whether in vivo brain levels of γ-aminobutyric acid (GABA), N-acetylaspartate (NAA), and other brain metabolites in male smelters were altered as a consequence of Mn exposure. Methods: We used T1-weighted magnetic resonance imaging (MRI) to visualize Mn deposition in the brain. Magnetic resonance spectroscopy (MRS) was used to quantify concentrations of NAA, glutamate, and other brain metabolites in globus pallidus, putamen, thalamus, and frontal cortex from a well-established cohort of 10 male Mn-exposed smelters and 10 male age-matched control subjects. We used the MEGA-PRESS MRS sequence to determine GABA levels in a region encompassing the thalamus and adjacent parts of the basal ganglia [GABA-VOI (volume of interest)].Results: Seven of 10 exposed subjects showed clear T1-hyperintense signals in the globus pallidus indicating Mn accumulation. We found a significant increase (82%; p = 0.014) in the ratio of GABA to total creatine (GABA/tCr) in the GABA-VOI of Mn-exposed subjects, as well as a distinct decrease (9%; p = 0.04) of NAA/tCr in frontal cortex that strongly correlated with cumulative Mn exposure (R = -0.93; p < 0.001).Conclusions: We demonstrated elevated GABA levels in the thalamus and adjacent basal ganglia and decreased NAA levels in the frontal cortex, indicating neuronal dysfunction in a brain area not primarily targeted by Mn. Therefore, the noninvasive in vivo MRS measurement of GABA and NAA may prove to be a powerful tool for detecting presymptomatic effects of Mn neurotoxicity.

Original languageEnglish
Pages (from-to)219-224
Number of pages6
JournalEnvironmental Health Perspectives
Volume119
Issue number2
DOIs
StatePublished - Feb 2011

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Manganese
gamma-Aminobutyric Acid
Magnetic Resonance Spectroscopy
Brain
Frontal Lobe
Thalamus
Globus Pallidus
Basal Ganglia
Aminobutyrates
Creatine
Putamen
Psychiatry
Glutamic Acid
Magnetic Resonance Imaging
N-acetylaspartate

Keywords

  • GABA
  • Imaging
  • Manganese
  • Metabolism
  • MRI
  • MRS
  • NAA
  • Occupational health
  • Parkinsonism
  • Smelters

ASJC Scopus subject areas

  • Health, Toxicology and Mutagenesis
  • Public Health, Environmental and Occupational Health

Cite this

In vivo measurement of brain GABA concentrations by magnetic resonance spectroscopy in smelters occupationally exposed to manganese. / Dydak, Ulrike; Jiang, Yue Ming; Long, Li Ling; Zhu, He; Chen, Jian; Li, Wen Mei; Edden, Richard A E; Hu, Shuguang; Fu, Xue; Long, Zaiyang; Mo, Xue An; Meier, Dieter; Harezlak, Jaroslaw; Aschner, Michael; Murdoch, James B.; Zheng, Wei.

In: Environmental Health Perspectives, Vol. 119, No. 2, 02.2011, p. 219-224.

Research output: Contribution to journalArticle

Dydak, U, Jiang, YM, Long, LL, Zhu, H, Chen, J, Li, WM, Edden, RAE, Hu, S, Fu, X, Long, Z, Mo, XA, Meier, D, Harezlak, J, Aschner, M, Murdoch, JB & Zheng, W 2011, 'In vivo measurement of brain GABA concentrations by magnetic resonance spectroscopy in smelters occupationally exposed to manganese', Environmental Health Perspectives, vol. 119, no. 2, pp. 219-224. https://doi.org/10.1289/ehp.1002192
Dydak, Ulrike ; Jiang, Yue Ming ; Long, Li Ling ; Zhu, He ; Chen, Jian ; Li, Wen Mei ; Edden, Richard A E ; Hu, Shuguang ; Fu, Xue ; Long, Zaiyang ; Mo, Xue An ; Meier, Dieter ; Harezlak, Jaroslaw ; Aschner, Michael ; Murdoch, James B. ; Zheng, Wei. / In vivo measurement of brain GABA concentrations by magnetic resonance spectroscopy in smelters occupationally exposed to manganese. In: Environmental Health Perspectives. 2011 ; Vol. 119, No. 2. pp. 219-224.
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abstract = "Background: Exposure to excessive levels of manganese (Mn) is known to induce psychiatric and motor disorders, including parkinsonian symptoms. Therefore, finding a reliable means for early detection of Mn neurotoxicity is desirable. Objectives: Our goal was to determine whether in vivo brain levels of γ-aminobutyric acid (GABA), N-acetylaspartate (NAA), and other brain metabolites in male smelters were altered as a consequence of Mn exposure. Methods: We used T1-weighted magnetic resonance imaging (MRI) to visualize Mn deposition in the brain. Magnetic resonance spectroscopy (MRS) was used to quantify concentrations of NAA, glutamate, and other brain metabolites in globus pallidus, putamen, thalamus, and frontal cortex from a well-established cohort of 10 male Mn-exposed smelters and 10 male age-matched control subjects. We used the MEGA-PRESS MRS sequence to determine GABA levels in a region encompassing the thalamus and adjacent parts of the basal ganglia [GABA-VOI (volume of interest)].Results: Seven of 10 exposed subjects showed clear T1-hyperintense signals in the globus pallidus indicating Mn accumulation. We found a significant increase (82{\%}; p = 0.014) in the ratio of GABA to total creatine (GABA/tCr) in the GABA-VOI of Mn-exposed subjects, as well as a distinct decrease (9{\%}; p = 0.04) of NAA/tCr in frontal cortex that strongly correlated with cumulative Mn exposure (R = -0.93; p < 0.001).Conclusions: We demonstrated elevated GABA levels in the thalamus and adjacent basal ganglia and decreased NAA levels in the frontal cortex, indicating neuronal dysfunction in a brain area not primarily targeted by Mn. Therefore, the noninvasive in vivo MRS measurement of GABA and NAA may prove to be a powerful tool for detecting presymptomatic effects of Mn neurotoxicity.",
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T1 - In vivo measurement of brain GABA concentrations by magnetic resonance spectroscopy in smelters occupationally exposed to manganese

AU - Dydak, Ulrike

AU - Jiang, Yue Ming

AU - Long, Li Ling

AU - Zhu, He

AU - Chen, Jian

AU - Li, Wen Mei

AU - Edden, Richard A E

AU - Hu, Shuguang

AU - Fu, Xue

AU - Long, Zaiyang

AU - Mo, Xue An

AU - Meier, Dieter

AU - Harezlak, Jaroslaw

AU - Aschner, Michael

AU - Murdoch, James B.

AU - Zheng, Wei

PY - 2011/2

Y1 - 2011/2

N2 - Background: Exposure to excessive levels of manganese (Mn) is known to induce psychiatric and motor disorders, including parkinsonian symptoms. Therefore, finding a reliable means for early detection of Mn neurotoxicity is desirable. Objectives: Our goal was to determine whether in vivo brain levels of γ-aminobutyric acid (GABA), N-acetylaspartate (NAA), and other brain metabolites in male smelters were altered as a consequence of Mn exposure. Methods: We used T1-weighted magnetic resonance imaging (MRI) to visualize Mn deposition in the brain. Magnetic resonance spectroscopy (MRS) was used to quantify concentrations of NAA, glutamate, and other brain metabolites in globus pallidus, putamen, thalamus, and frontal cortex from a well-established cohort of 10 male Mn-exposed smelters and 10 male age-matched control subjects. We used the MEGA-PRESS MRS sequence to determine GABA levels in a region encompassing the thalamus and adjacent parts of the basal ganglia [GABA-VOI (volume of interest)].Results: Seven of 10 exposed subjects showed clear T1-hyperintense signals in the globus pallidus indicating Mn accumulation. We found a significant increase (82%; p = 0.014) in the ratio of GABA to total creatine (GABA/tCr) in the GABA-VOI of Mn-exposed subjects, as well as a distinct decrease (9%; p = 0.04) of NAA/tCr in frontal cortex that strongly correlated with cumulative Mn exposure (R = -0.93; p < 0.001).Conclusions: We demonstrated elevated GABA levels in the thalamus and adjacent basal ganglia and decreased NAA levels in the frontal cortex, indicating neuronal dysfunction in a brain area not primarily targeted by Mn. Therefore, the noninvasive in vivo MRS measurement of GABA and NAA may prove to be a powerful tool for detecting presymptomatic effects of Mn neurotoxicity.

AB - Background: Exposure to excessive levels of manganese (Mn) is known to induce psychiatric and motor disorders, including parkinsonian symptoms. Therefore, finding a reliable means for early detection of Mn neurotoxicity is desirable. Objectives: Our goal was to determine whether in vivo brain levels of γ-aminobutyric acid (GABA), N-acetylaspartate (NAA), and other brain metabolites in male smelters were altered as a consequence of Mn exposure. Methods: We used T1-weighted magnetic resonance imaging (MRI) to visualize Mn deposition in the brain. Magnetic resonance spectroscopy (MRS) was used to quantify concentrations of NAA, glutamate, and other brain metabolites in globus pallidus, putamen, thalamus, and frontal cortex from a well-established cohort of 10 male Mn-exposed smelters and 10 male age-matched control subjects. We used the MEGA-PRESS MRS sequence to determine GABA levels in a region encompassing the thalamus and adjacent parts of the basal ganglia [GABA-VOI (volume of interest)].Results: Seven of 10 exposed subjects showed clear T1-hyperintense signals in the globus pallidus indicating Mn accumulation. We found a significant increase (82%; p = 0.014) in the ratio of GABA to total creatine (GABA/tCr) in the GABA-VOI of Mn-exposed subjects, as well as a distinct decrease (9%; p = 0.04) of NAA/tCr in frontal cortex that strongly correlated with cumulative Mn exposure (R = -0.93; p < 0.001).Conclusions: We demonstrated elevated GABA levels in the thalamus and adjacent basal ganglia and decreased NAA levels in the frontal cortex, indicating neuronal dysfunction in a brain area not primarily targeted by Mn. Therefore, the noninvasive in vivo MRS measurement of GABA and NAA may prove to be a powerful tool for detecting presymptomatic effects of Mn neurotoxicity.

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KW - Imaging

KW - Manganese

KW - Metabolism

KW - MRI

KW - MRS

KW - NAA

KW - Occupational health

KW - Parkinsonism

KW - Smelters

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