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In Vivo Measurement of Brain GABA Concentrations by Magnetic Resonance Spectroscopy in Smelters Occupationally Exposed to Manganese


Dydak, U; Jiang, Y M; Long, L L; Zhu, H; Chen, J; Li, W M; Edden, R A E; Hu, S; Fu, X; Long, Z; Mo, X A; Meier, D; Harezlak, J; Aschner, M; Murdoch, J B; Zheng, W (2011). In Vivo Measurement of Brain GABA Concentrations by Magnetic Resonance Spectroscopy in Smelters Occupationally Exposed to Manganese. Environmental health perspectives, 119(2):219-224.

Abstract

Background: Exposure to excessive manganese (Mn) levels 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 study whether in-vivo brain levels of gamma-aminobutyric acid (GABA), N-acetylaspartate (NAA) and other brain metabolites in smelters were altered as a consequence of Mn exposure. Methods: T1-weighted MRI was used 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. The MEGA-PRESS MRS sequence was used to determine GABA levels in a region encompassing the thalamus and adjacent parts of the basal ganglia ("GABA-VOI"). Results: Seven out of ten exposed subjects showed clear T1-hyperintense signals in the globus pallidus indicating Mn accumulation. We found a significant increase (82%; p=0.014) of 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 (R= - 0.93, p<0.001) with cumulative Mn exposure. Conclusions: We demonstrated elevated GABA levels in the thalamus and adjacent basal ganglia and decreased frontal cortex NAA levels, indicating neuronal dysfunction in a brain area not primarily targeted by Mn. Therefore, the non-invasive in vivo MRS measurement of GABA and NAA may prove to be a powerful tool for detecting presymptomatic effects of Mn neurotoxicity.

Background: Exposure to excessive manganese (Mn) levels 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 study whether in-vivo brain levels of gamma-aminobutyric acid (GABA), N-acetylaspartate (NAA) and other brain metabolites in smelters were altered as a consequence of Mn exposure. Methods: T1-weighted MRI was used 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. The MEGA-PRESS MRS sequence was used to determine GABA levels in a region encompassing the thalamus and adjacent parts of the basal ganglia ("GABA-VOI"). Results: Seven out of ten exposed subjects showed clear T1-hyperintense signals in the globus pallidus indicating Mn accumulation. We found a significant increase (82%; p=0.014) of 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 (R= - 0.93, p<0.001) with cumulative Mn exposure. Conclusions: We demonstrated elevated GABA levels in the thalamus and adjacent basal ganglia and decreased frontal cortex NAA levels, indicating neuronal dysfunction in a brain area not primarily targeted by Mn. Therefore, the non-invasive 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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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Biomedical Engineering
Dewey Decimal Classification:170 Ethics
610 Medicine & health
Language:English
Date:2011
Deposited On:05 Jan 2011 06:16
Last Modified:05 Apr 2016 14:32
Publisher:The National Institute of Environmental Health Sciences (NIEHS)
ISSN:0091-6765
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:10.1289/ehp.1002192
PubMed ID:20876035
Permanent URL: http://doi.org/10.5167/uzh-41403

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