Thalamic GABA levels and occupational manganese neurotoxicity: Association with exposure levels and brain MRI

Ruoyun E. Ma, Eric J. Ward, Chien Lin Yeh, Sandy Snyder, Zaiyang Long, Fulya Gokalp Yavuz, S. Zauber, Ulrike Dydak

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Excessive occupational exposure to Manganese (Mn) has been associated with clinical symptoms resembling idiopathic Parkinson's disease (IPD), impairing cognitive and motor functions. Several studies point towards an involvement of the brain neurotransmitter system in Mn intoxication, which is hypothesized to be disturbed prior to onset of symptoms. Edited Magnetic Resonance Spectroscopy (MRS) offers the unique possibility to measure γ-amminobutyric acid (GABA) and other neurometabolites in vivo non-invasively in workers exposed to Mn. In addition, the property of Mn as Magnetic Resonance Imaging (MRI) contrast agent may be used to study Mn deposition in the human brain. In this study, using MRI, MRS, personal air sampling at the working place, work history questionnaires, and neurological assessment (UPDRS-III), the effects of chronic Mn exposure on the thalamic GABAergic system was studied in a group of welders (N=39) with exposure to Mn fumes in a typical occupational setting. Two subgroups of welders with different exposure levels (Low: N=26; mean air Mn=0.13±0.1mg/m3; High: N=13; mean air Mn=0.23±0.18mg/m3), as well as unexposed control workers (N=22, mean air Mn=0.002±0.001mg/m3) were recruited. The group of welders with higher exposure showed a significant increase of thalamic GABA levels by 45% (p<0.01, F(1,33)=9.55), as well as significantly worse performance in general motor function (p<0.01, F(1,33)=11.35). However, welders with lower exposure did not differ from the controls in GABA levels or motor performance. Further, in welders the thalamic GABA levels were best predicted by past-12-months exposure levels and were influenced by the Mn deposition in the substantia nigra and globus pallidus. Importantly, both thalamic GABA levels and motor function displayed a non-linear pattern of response to Mn exposure, suggesting a threshold effect.

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

Fingerprint

Manganese
gamma-Aminobutyric Acid
Brain
Magnetic Resonance Imaging
Air
Magnetic resonance spectroscopy
Magnetic Resonance Spectroscopy
Fumes
Globus Pallidus
Substantia Nigra
Occupational Exposure
Workplace
Cognition
Contrast Media
Neurotransmitter Agents
Parkinson Disease
Sampling

Keywords

  • Magnetic resonance spectroscopy
  • Manganese neurotoxicity
  • MRI
  • Rigidity
  • Thalamus
  • Welding
  • γ-aminobutyric acid (GABA)

ASJC Scopus subject areas

  • Neuroscience(all)
  • Toxicology

Cite this

Ma, R. E., Ward, E. J., Yeh, C. L., Snyder, S., Long, Z., Gokalp Yavuz, F., ... Dydak, U. (Accepted/In press). Thalamic GABA levels and occupational manganese neurotoxicity: Association with exposure levels and brain MRI. NeuroToxicology. https://doi.org/10.1016/j.neuro.2017.08.013

Thalamic GABA levels and occupational manganese neurotoxicity : Association with exposure levels and brain MRI. / Ma, Ruoyun E.; Ward, Eric J.; Yeh, Chien Lin; Snyder, Sandy; Long, Zaiyang; Gokalp Yavuz, Fulya; Zauber, S.; Dydak, Ulrike.

In: NeuroToxicology, 2017.

Research output: Contribution to journalArticle

Ma, Ruoyun E. ; Ward, Eric J. ; Yeh, Chien Lin ; Snyder, Sandy ; Long, Zaiyang ; Gokalp Yavuz, Fulya ; Zauber, S. ; Dydak, Ulrike. / Thalamic GABA levels and occupational manganese neurotoxicity : Association with exposure levels and brain MRI. In: NeuroToxicology. 2017.
@article{4d929d0efb444976b29dbaf0201b992d,
title = "Thalamic GABA levels and occupational manganese neurotoxicity: Association with exposure levels and brain MRI",
abstract = "Excessive occupational exposure to Manganese (Mn) has been associated with clinical symptoms resembling idiopathic Parkinson's disease (IPD), impairing cognitive and motor functions. Several studies point towards an involvement of the brain neurotransmitter system in Mn intoxication, which is hypothesized to be disturbed prior to onset of symptoms. Edited Magnetic Resonance Spectroscopy (MRS) offers the unique possibility to measure γ-amminobutyric acid (GABA) and other neurometabolites in vivo non-invasively in workers exposed to Mn. In addition, the property of Mn as Magnetic Resonance Imaging (MRI) contrast agent may be used to study Mn deposition in the human brain. In this study, using MRI, MRS, personal air sampling at the working place, work history questionnaires, and neurological assessment (UPDRS-III), the effects of chronic Mn exposure on the thalamic GABAergic system was studied in a group of welders (N=39) with exposure to Mn fumes in a typical occupational setting. Two subgroups of welders with different exposure levels (Low: N=26; mean air Mn=0.13±0.1mg/m3; High: N=13; mean air Mn=0.23±0.18mg/m3), as well as unexposed control workers (N=22, mean air Mn=0.002±0.001mg/m3) were recruited. The group of welders with higher exposure showed a significant increase of thalamic GABA levels by 45{\%} (p<0.01, F(1,33)=9.55), as well as significantly worse performance in general motor function (p<0.01, F(1,33)=11.35). However, welders with lower exposure did not differ from the controls in GABA levels or motor performance. Further, in welders the thalamic GABA levels were best predicted by past-12-months exposure levels and were influenced by the Mn deposition in the substantia nigra and globus pallidus. Importantly, both thalamic GABA levels and motor function displayed a non-linear pattern of response to Mn exposure, suggesting a threshold effect.",
keywords = "Magnetic resonance spectroscopy, Manganese neurotoxicity, MRI, Rigidity, Thalamus, Welding, γ-aminobutyric acid (GABA)",
author = "Ma, {Ruoyun E.} and Ward, {Eric J.} and Yeh, {Chien Lin} and Sandy Snyder and Zaiyang Long and {Gokalp Yavuz}, Fulya and S. Zauber and Ulrike Dydak",
year = "2017",
doi = "10.1016/j.neuro.2017.08.013",
language = "English (US)",
journal = "NeuroToxicology",
issn = "0161-813X",
publisher = "Elsevier",

}

TY - JOUR

T1 - Thalamic GABA levels and occupational manganese neurotoxicity

T2 - Association with exposure levels and brain MRI

AU - Ma, Ruoyun E.

AU - Ward, Eric J.

AU - Yeh, Chien Lin

AU - Snyder, Sandy

AU - Long, Zaiyang

AU - Gokalp Yavuz, Fulya

AU - Zauber, S.

AU - Dydak, Ulrike

PY - 2017

Y1 - 2017

N2 - Excessive occupational exposure to Manganese (Mn) has been associated with clinical symptoms resembling idiopathic Parkinson's disease (IPD), impairing cognitive and motor functions. Several studies point towards an involvement of the brain neurotransmitter system in Mn intoxication, which is hypothesized to be disturbed prior to onset of symptoms. Edited Magnetic Resonance Spectroscopy (MRS) offers the unique possibility to measure γ-amminobutyric acid (GABA) and other neurometabolites in vivo non-invasively in workers exposed to Mn. In addition, the property of Mn as Magnetic Resonance Imaging (MRI) contrast agent may be used to study Mn deposition in the human brain. In this study, using MRI, MRS, personal air sampling at the working place, work history questionnaires, and neurological assessment (UPDRS-III), the effects of chronic Mn exposure on the thalamic GABAergic system was studied in a group of welders (N=39) with exposure to Mn fumes in a typical occupational setting. Two subgroups of welders with different exposure levels (Low: N=26; mean air Mn=0.13±0.1mg/m3; High: N=13; mean air Mn=0.23±0.18mg/m3), as well as unexposed control workers (N=22, mean air Mn=0.002±0.001mg/m3) were recruited. The group of welders with higher exposure showed a significant increase of thalamic GABA levels by 45% (p<0.01, F(1,33)=9.55), as well as significantly worse performance in general motor function (p<0.01, F(1,33)=11.35). However, welders with lower exposure did not differ from the controls in GABA levels or motor performance. Further, in welders the thalamic GABA levels were best predicted by past-12-months exposure levels and were influenced by the Mn deposition in the substantia nigra and globus pallidus. Importantly, both thalamic GABA levels and motor function displayed a non-linear pattern of response to Mn exposure, suggesting a threshold effect.

AB - Excessive occupational exposure to Manganese (Mn) has been associated with clinical symptoms resembling idiopathic Parkinson's disease (IPD), impairing cognitive and motor functions. Several studies point towards an involvement of the brain neurotransmitter system in Mn intoxication, which is hypothesized to be disturbed prior to onset of symptoms. Edited Magnetic Resonance Spectroscopy (MRS) offers the unique possibility to measure γ-amminobutyric acid (GABA) and other neurometabolites in vivo non-invasively in workers exposed to Mn. In addition, the property of Mn as Magnetic Resonance Imaging (MRI) contrast agent may be used to study Mn deposition in the human brain. In this study, using MRI, MRS, personal air sampling at the working place, work history questionnaires, and neurological assessment (UPDRS-III), the effects of chronic Mn exposure on the thalamic GABAergic system was studied in a group of welders (N=39) with exposure to Mn fumes in a typical occupational setting. Two subgroups of welders with different exposure levels (Low: N=26; mean air Mn=0.13±0.1mg/m3; High: N=13; mean air Mn=0.23±0.18mg/m3), as well as unexposed control workers (N=22, mean air Mn=0.002±0.001mg/m3) were recruited. The group of welders with higher exposure showed a significant increase of thalamic GABA levels by 45% (p<0.01, F(1,33)=9.55), as well as significantly worse performance in general motor function (p<0.01, F(1,33)=11.35). However, welders with lower exposure did not differ from the controls in GABA levels or motor performance. Further, in welders the thalamic GABA levels were best predicted by past-12-months exposure levels and were influenced by the Mn deposition in the substantia nigra and globus pallidus. Importantly, both thalamic GABA levels and motor function displayed a non-linear pattern of response to Mn exposure, suggesting a threshold effect.

KW - Magnetic resonance spectroscopy

KW - Manganese neurotoxicity

KW - MRI

KW - Rigidity

KW - Thalamus

KW - Welding

KW - γ-aminobutyric acid (GABA)

UR - http://www.scopus.com/inward/record.url?scp=85029227217&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85029227217&partnerID=8YFLogxK

U2 - 10.1016/j.neuro.2017.08.013

DO - 10.1016/j.neuro.2017.08.013

M3 - Article

C2 - 28873337

AN - SCOPUS:85029227217

JO - NeuroToxicology

JF - NeuroToxicology

SN - 0161-813X

ER -