title: In vivo measurement of brain GABA concentrations by magnetic resonance spectroscopy in smelters occupationally exposed to manganese.
abstract: 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.
  
  
  OBJECTIVE
  Our goal was to determine whether in vivo brain levels of γ-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 T1-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 neurotoxicity.
authors.affiliation: School of Health Sciences, Purdue University, West Lafayette, Indiana 47907, USA. udydak@purdue.edu
authors.forename: Ulrike
authors.initials: U
authors.lastname: Dydak
authors.forename: Yue-Ming
authors.initials: YM
authors.lastname: Jiang
authors.forename: Li-Ling
authors.initials: LL
authors.lastname: Long
authors.forename: He
authors.initials: H
authors.lastname: Zhu
authors.forename: Jian
authors.initials: J
authors.lastname: Chen
authors.forename: Wen-Mei
authors.initials: WM
authors.lastname: Li
authors.forename: Richard A E
authors.initials: RA
authors.lastname: Edden
authors.forename: Shuguang
authors.initials: S
authors.lastname: Hu
authors.forename: Xue
authors.initials: X
authors.lastname: Fu
authors.forename: Zaiyang
authors.initials: Z
authors.lastname: Long
authors.forename: Xue-An
authors.initials: XA
authors.lastname: Mo
authors.forename: Dieter
authors.initials: D
authors.lastname: Meier
authors.forename: Jaroslaw
authors.initials: J
authors.lastname: Harezlak
authors.forename: Michael
authors.initials: M
authors.lastname: Aschner
authors.forename: James B
authors.initials: JB
authors.lastname: Murdoch
authors.forename: Wei
authors.initials: W
authors.lastname: Zheng
mesh_terms: D000328:Adult; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008297:Male; D008345:Manganese / Q000633:toxicity*; D008875:Middle Aged; D016273:Occupational Exposure / Q000009:adverse effects; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D008345:Manganese; D005680:gamma-Aminobutyric Acid