title: Thalamic GABA predicts fine motor performance in manganese-exposed smelter workers.
abstract: Overexposure to manganese (Mn) may lead to parkinsonian symptoms including motor deficits. The main inhibitory neurotransmitter gamma-aminobutyric acid (GABA) is known to play a pivotal role in the regulation and performance of movement. Therefore this study was aimed at testing the hypothesis that an alteration of GABA following Mn exposure may be associated with fine motor performance in occupationally exposed workers and may underlie the mechanism of Mn-induced motor deficits. A cohort of nine Mn-exposed male smelter workers from an Mn-iron alloy factory and 23 gender- and age-matched controls were recruited and underwent neurological exams, magnetic resonance spectroscopy (MRS) measurements, and Purdue pegboard motor testing. Short-echo-time MRS was used to measure N-Acetyl-aspartate (NAA) and myo-inositol (mI). GABA was detected with a MEGA-PRESS J-editing MRS sequence. The mean thalamic GABA level was significantly increased in smelter workers compared to controls (p = 0.009). Multiple linear regression analysis reveals (1) a significant association between the increase in GABA level and the duration of exposure (R(2) = 0.660, p = 0.039), and (2) significant inverse associations between GABA levels and all Purdue pegboard test scores (for summation of all scores R(2) = 0.902, p = 0.001) in the smelter workers. In addition, levels of mI were reduced significantly in the thalamus and PCC of smelter workers compared to controls (p = 0.030 and p = 0.009, respectively). In conclusion, our results show clear associations between thalamic GABA levels and fine motor performance. Thus in Mn-exposed subjects, increased thalamic GABA levels may serve as a biomarker for subtle deficits in motor control and may become valuable for early diagnosis of Mn poisoning.
authors: School of Health Sciences, Purdue University, West Lafayette, Indiana, United States of America ; Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, Indiana, United States of America.
authors: Zaiyang
authors: Z
authors: Long
authors: Department of Radiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.
authors: Xiang-Rong
authors: XR
authors: Li
authors: School of Health Sciences, Purdue University, West Lafayette, Indiana, United States of America ; Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, Indiana, United States of America.
authors: Jun
authors: J
authors: Xu
authors: Russell H. Morgan Department of Radiology and Radiological Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America ; FM Kirby Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, Maryland, United States of America.
authors: Richard A E
authors: RA
authors: Edden
authors: Department of Occupational Poisoning, Guangxi Institute for Occupational Disease Prevention and Treatment, Nanning, China.
authors: Wei-Ping
authors: WP
authors: Qin
authors: Department of Radiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.
authors: Li-Ling
authors: LL
authors: Long
authors: Toshiba Medical Research Institute USA, Mayfield Village, Ohio, United States of America.
authors: James B
authors: JB
authors: Murdoch
authors: School of Health Sciences, Purdue University, West Lafayette, Indiana, United States of America.
authors: Wei
authors: W
authors: Zheng
authors: Department of Health Toxicology, Guangxi Medical University, Nanning, China.
authors: Yue-Ming
authors: YM
authors: Jiang
authors: School of Health Sciences, Purdue University, West Lafayette, Indiana, United States of America ; Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, Indiana, United States of America.
authors: Ulrike
authors: U
authors: Dydak
mesh_terms: D000328:Adult; D006801:Humans; D007501:Iron / Q000009:adverse effects*; D008297:Male; D008345:Manganese / Q000009:adverse effects*; D009043:Motor Activity / Q000502:physiology*; D009460:Neurologic Examination / Q000379:methods; D016273:Occupational Exposure / Q000009:adverse effects*; D013788:Thalamus / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: C083456:ferro-manganese alloy; D008345:Manganese; D005680:gamma-Aminobutyric Acid; D007501:Iron