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

被引:120
作者
Dydak, Ulrike [1 ,2 ]
Jiang, Yue-Ming [3 ]
Long, Li-Ling [4 ]
Zhu, He [5 ,6 ]
Chen, Jian [7 ]
Li, Wen-Mei [4 ]
Edden, Richard A. E. [5 ,6 ]
Hu, Shuguang [8 ]
Fu, Xue [1 ]
Long, Zaiyang [1 ]
Mo, Xue-An [9 ]
Meier, Dieter [10 ,11 ]
Harezlak, Jaroslaw [12 ]
Aschner, Michael [13 ]
Murdoch, James B. [14 ]
Zheng, Wei [1 ]
机构
[1] Purdue Univ, Sch Hlth Sci, W Lafayette, IN 47907 USA
[2] Indiana Univ Sch Med, Dept Radiol & Imaging Sci, Indianapolis, IN USA
[3] Guangxi Med Univ, Sch Publ Hlth, Dept Hlth Toxicol, Nanning, Peoples R China
[4] Guangxi Med Univ, Affiliated Hosp 1, Dept Radiol, Nanning, Peoples R China
[5] Johns Hopkins Univ Sch Med, Russell H Morgan Dept Radiol & Radiol Sci, Baltimore, MD USA
[6] Kennedy Krieger Inst, FM Kirby Res Ctr Funct Brain Imaging, Baltimore, MD USA
[7] Guizhou Inst Occupat Safety & Hlth, Zunyi, Peoples R China
[8] Philips Healthcare, Clin Sci, Guangzhou, Guangdong, Peoples R China
[9] Guangxi Med Univ, Affiliated Hosp 1, Dept Neurol, Nanning, Peoples R China
[10] Univ Zurich, Inst Biomed Engn, Zurich, Switzerland
[11] ETH, Zurich, Switzerland
[12] Indiana Univ Sch Med, Div Biostat, Indianapolis, IN USA
[13] Vanderbilt Univ, Dept Pediat, Nashville, TN USA
[14] Toshiba Med Res Inst USA, Mayfield Village, OH USA
基金
美国国家卫生研究院;
关键词
GABA; imaging; manganese; metabolism; MRI; MRS; NAA; occupational health; parkinsonism; smelters; GAMMA-AMINOBUTYRIC-ACID; NONHUMAN PRIMATE BRAIN; METABOLITE CONCENTRATIONS; IDIOPATHIC PARKINSONISM; SULFATE INHALATION; SMELTING WORKERS; BASAL GANGLIA; RAT-BRAIN; CORTEX; DOPAMINE;
D O I
10.1289/ehp.1002192
中图分类号
X [环境科学、安全科学];
学科分类号
08 ; 0830 ;
摘要
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.-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 T(1)-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 neuro-toxicity.
引用
收藏
页码:219 / 224
页数:6
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