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 (R2 = 0.660, p = 0.039), and (2) significant inverse associations between GABA levels and all Purdue pegboard test scores (for summation of all scores R2 = 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.

Striatal and thalamic GABA level concentrations play differential roles for the modulation of response selection processes by proprioceptive information

“…High resolution 3D T1-weighted Magnetization Prepared - Rapid Gradient Echo (MP-RAGE) images were also obtained for brain tissue segmentation into white matter (WM), grey matter (GM) and cerebrospinal fluid (CSF). The right hemisphere was chosen in order to be consistent with our earlier studies on manganism (Dydak et al, 2011; Long et al, 2014). Higher order shimming was performed either manually or using FASTMAP (Gruetter, 1993) to achieve a spectral linewidth of < 25 Hz.…”

Manganese Toxicity Upon Overexposure: a Decade in Review

“…Changes in thalamic GABA were associated with reduced fine motor performance as assessed by the Purdue Pegboard test [98]. …”

Vulnerability of welders to manganese exposure – A neuroimaging study

“…Brain Fe concentration is known to be elevated in the substantia nigra, globus pallidus and caudate of patients with Parkinson’s disease (Dexter et al, 1987; Griffiths and Grossman, 1993; Batista-Nascimento et al, 2012; Rossi et al, 2014); however, it is much less studied in Mn-exposed workers. Several MRS studies have investigated Mn-induced neurochemical changes and some of the results seem to be inconsistent, such as decreased or no change of frontal N-acetyl aspartate (NAA) (Guilarte et al, 2006; Kim et al, 2007; Chang et al, 2009; Dydak et al, 2011; Long et al, 2014). In this study we present data on the effect of Mn exposure on metabolite levels, T1 signal hyperintensities and T2* values in two cortical and two deep brain regions for two different occupational settings with Mn exposure: welding and smelting.…”