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GABA levels correlate with exposure levels and brain deposition of manganese in US welders.

Ma R; Yeh C; Ward EJ; Long Z; Murdoch JB; Snyder S; Zauber E; Rosenthal F; Dydak U
Toxicologist 2014 Mar; 138(1):366-367
Excessive manganese (Mn) exposure has been associated with decline in cognitive and motor function. Our previous study in a cohort of highly Mn-exposed Chinese workers found significantly elevated thalamic gamma-aminobutyric acid (GABA) levels. The current study explored the relationships among brain GABA levels measured in vivo by magnetic resonance spectroscopy (MRS), brain Mn deposition measured by MRI and individual Mn exposure levels in a typical US occupational setting. Thirteen welders and eleven controls were recruited from a US truck trailer manufacturer. Subjects underwent personal air sampling and filled out a questionnaire of detailed work history for the estimation of individual exposure to respirable Mn. For each subject a series of 3D images were acquired on a 3T GE Signa MRI scanner and used to create high-resolution T1 relaxation maps, an inverse indicator of Mn deposition. GABA spectra were acquired from the thalamus with a TE68 MEGA-PRESS sequence and quantified using LCModel, a spectral fitting tool. GABA levels were significantly higher in welders vs. controls [2.45+/-0.68 mM vs. 1.40+/-0.45 mM, p<0.001]. Increased thalamic GABA levels significantly correlated with (a) average exposure estimated for the previous three months before the MRI exam [R=0.649, p<0.05] and with (b) decreased T1 relaxation time in the substantia nigra, denoting increased Mn deposition [R=-0.589, p<0.05]. These results confirm the elevation of thalamic GABA levels in a typical US occupational setting. The significant correlations between increased GABA levels and recent exposure levels, as well as with brain Mn accumulation in the substantia nigra, suggest that GABA-edited MRS in conjunction with quantitative T1 relaxation MRI may serve as a biomarker of Mn exposure.
Toxicology; Workers; Work-environment; Humans; Men; Women; Environmental-exposure; Environmental-hazards; Environmental-health; Metal-compounds; Metallic-compounds; Welding; Welding-industry; Welders; Exposure-levels
7440-43-9; 7440-47-3
Publication Date
Document Type
Funding Type
Fiscal Year
Identifying No.
Grant-Number-T03-OH-008615; M032014
Issue of Publication
Source Name
The Toxicologist. Society of Toxicology 53rd Annual Meeting and ToxExpo, March 23-27, 2014, Phonex, Arizona
Performing Organization
Purdue University, West Lafayette, Indiana
Page last reviewed: April 8, 2022
Content source: National Institute for Occupational Safety and Health Education and Information Division