Objective

Magnetic resonance spectroscopy (MRS) is a non-invasive method to quantify neurometabolite concentrations in the brain. Within the framework of the WELDOX II study, we investigated the association of exposure to manganese (Mn) and iron (Fe) with γ-aminobutyric acid (GABA) and other neurometabolites in the striatum and thalamus of 154 men.

Material and methods

GABA-edited and short echo-time MRS at 3T was used to assess brain levels of GABA, glutamate, total creatine (tCr) and other neurometabolites. Volumes of interest (VOIs) were placed into the striatum and thalamus of both hemispheres of 47 active welders, 20 former welders, 36 men with Parkinson’s disease (PD), 12 men with hemochromatosis (HC), and 39 male controls. Linear mixed models were used to estimate the influence of Mn and Fe exposure on neurometabolites while simultaneously adjusting for cerebrospinal fluid (CSF) content, age and other factors. Exposure to Mn and Fe was assessed by study group, blood concentrations, relaxation rates R1 and R2* in the globus pallidus (GP), and airborne exposure (active welders only).

Results

The median shift exposure to respirable Mn and Fe in active welders was 23 μg/m³ and 110 μg/m³, respectively. Airborne exposure was not associated with any other neurometabolite concentration. Mn in blood and serum ferritin were highest in active and former welders. GABA concentrations were not associated with any measure of exposure to Mn or Fe. In comparison to controls, tCr in these VOIs was lower in welders and patients with PD or HC. Serum concentrations of ferritin and Fe were associated with N-acetylaspartate, but in opposed directions. Higher R1 values in the GP correlated with lower neurometabolite concentrations, in particular tCr (exp(β) = 0.87, p < 0.01) and choline (exp(β) = 0.84, p = 0.04). R2* was positively associated with glutamate-glutamine and negatively with myo-inositol.

Conclusions

Our results do not provide evidence that striatal and thalamic GABA differ between Mn-exposed workers, PD or HC patients, and controls. This may be due to the low exposure levels of the Mn-exposed workers and the challenges to detect small changes in GABA. Whereas Mn in blood was not associated with any neurometabolite content in these VOIs, a higher metal accumulation in the GP assessed with R1 correlated with generally lower neurometabolite concentrations.

中文翻译：

---

接触锰和铁与纹状体和丘脑 GABA 及其他神经代谢物的关联 — WELDOX II 研究的神经影像学结果

 客观的

磁共振波谱（MRS）是一种量化大脑中神经代谢物浓度的非侵入性方法。在 WELDOX II 研究的框架内，我们研究了 154 名男性纹状体和丘脑中接触锰 (Mn) 和铁 (Fe) 与 γ-氨基丁酸 (GABA) 和其他神经代谢物的关系。

 材料与方法

GABA 编辑的 3T 短回波时间 MRS 用于评估 GABA、谷氨酸、总肌酸 (tCr) 和其他神经代谢物的大脑水平。将感兴趣体积 (VOI) 放入 47 名现役焊工、20 名前焊工、36 名帕金森病 (PD) 男性、12 名血色素沉着症 (HC) 男性和 39 名男性对照者的两个半球纹状体和丘脑中。使用线性混合模型来估计锰和铁暴露对神经代谢物的影响，同时调整脑脊液（CSF）含量、年龄和其他因素。通过研究组、血液浓度、苍白球 (GP) 松弛率 R1 和 R2* 以及空气传播（仅限活跃焊工）评估锰和铁的暴露情况。

 结果

活跃焊工中可吸入锰和铁的中位偏移暴露分别为 23 μg/m ³和 110 μg/m ³ 。空气中的暴露与任何其他神经代谢物浓度无关。在职焊工和前焊工中，血液中的锰和血清铁蛋白含量最高。 GABA 浓度与任何锰或铁暴露量无关。与对照组相比，这些 VOI 中的 tCr 在焊工和 PD 或 HC 患者中较低。铁蛋白和 Fe 的血清浓度与N-乙酰天冬氨酸相关，但方向相反。 GP 中较高的 R1 值与较低的神经代谢物浓度相关，特别是 tCr（exp(β) = 0.87，p < 0.01）和胆碱（exp(β) = 0.84，p = 0.04）。 R2* 与谷氨酸-谷氨酰胺呈正相关，与肌醇呈负相关。

 结论

我们的结果没有提供证据表明接触锰的工人、PD 或 HC 患者以及对照组之间纹状体和丘脑 GABA 存在差异。这可能是由于接触锰的工人的接触水平较低以及检测 GABA 微小变化的挑战所致。虽然血液中的 Mn 与这些 VOI 中的任何神经代谢物含量无关，但用 R1 评估的 GP 中较高的金属积累与通常较低的神经代谢物浓度相关。