Thalamic GABA Levels and Occupational Manganese Neurotoxicity: Association with Exposure Levels and Brain MRI

Details

• Personal Author:
  Dydak U ; Gokalp Yavuz F ; Long Z ; Ma RE ; Snyder S ; Ward EJ ; Yeh C-L ; Zauber SE
• Description:
  Excessive occupational exposure to Manganese (Mn) has been associated with clinical symptoms resembling idiopathic Parkinson's disease (IPD), impairing cognitive and motor functions. Several studies point towards an involvement of the brain neurotransmitter system in Mn intoxication, which is hypothesized to be disturbed prior to onset of symptoms. Edited Magnetic Resonance Spectroscopy (MRS) offers the unique possibility to measure gamma-aminobutyric acid (GABA) and other neurometabolites in vivo non-invasively in workers exposed to Mn. In addition, the property of Mn as Magnetic Resonance Imaging (MRI) contrast agent may be used to study Mn deposition in the human brain. In this study, using MRI, MRS, personal air sampling at the working place, work history questionnaires, and neurological assessment (UPDRS-III), the effects of chronic Mn exposure on the thalamic GABAergic system was studied in a group of welders (N=39) with exposure to Mn fumes in a typical occupational setting. Two subgroups of welders with different exposure levels (Low: N=26; mean air Mn=0.13+/-0.1mg/m3; High: N=13; mean air Mn=0.23+/-0.18mg/m3), as well as unexposed control workers (N=22, mean air Mn=0.002+/-0.001mg/m3) were recruited. The group of welders with higher exposure showed a significant increase of thalamic GABA levels by 45% (p<0.01, F(1,33)=9.55), as well as significantly worse performance in general motor function (p<0.01, F(1,33)=11.35). However, welders with lower exposure did not differ from the controls in GABA levels or motor performance. Further, in welders the thalamic GABA levels were best predicted by past-12-months exposure levels and were influenced by the Mn deposition in the substantia nigra and globus pallidus. Importantly, both thalamic GABA levels and motor function displayed a non-linear pattern of response to Mn exposure, suggesting a threshold effect. [Description provided by NIOSH]
• Subjects:
  Environmental Exposure Environmental Monitoring Nervous System Occupational Exposure Occupational Health Safety Surveys And Questionnaires Welding
• Keywords:
  Air Sampling Amino Acids Author Keywords: Manganese Neurotoxicity Brain Function Brain Matter Chemical Deposition Chronic Exposure Clinical Symptoms Cognitive Function Exposure Assessment Exposure Levels G-aminobutyric Acid GABA Humans Imaging Techniques Magnetic Resonance Imaging Magnetic Resonance Spectroscopy Manganese Compounds MRI Neurological Reactions Neuromotor Function Neurotoxic Effects Neurotoxicity Neurotransmitters Parkinsonism Parkinsons Disease Performance Tests Questionnaires Rigidity Sensory Motor System Spectroscopes Thalamus Welders Welding Fumes Work Experience

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• ISSN:
  0161-813X
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  Indiana ; Minnesota ; OSHA Region 5
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  30-42
• Volume:
  64
• NIOSHTIC Number:
  nn:20054202
• Citation:
  Neurotoxicology 2018 Jan; 64:30-42
• Contact Point Address:
  Ulrike Dydak, School of Health Sciences, Purdue University, 550 Stadium Mall Drive, West Lafayette, IN 47907, USA
• Email:
  udydak@purdue.edu
• CAS Registry Number:
  Manganese (CAS RN 7439-96-5) ; y-Aminobutyric acid (CAS RN 56-12-2)
• Federal Fiscal Year:
  2018
• Performing Organization:
  Purdue University, West Lafayette, Indiana
• Peer Reviewed:
  True
• Start Date:
  20010701
• Source Full Name:
  Neurotoxicology
• End Date:
  20270630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:d4635651c0299691d650bc4684649d412d511621acf41067ea88683c20461dfe15bda54aef5ff2afad991567f7a2bcaa88ac27fe94ed971aad8d9aa24b402d81
• Download URL:
  https://stacks.cdc.gov/view/cdc/216814/cdc_216814_DS1.pdf
• File Type:
  [PDF - 2.36 MB ]