Aberration of Corticothalamic Brain Regions in Rats Exposed to Welding Fumes

Details

• Personal Author:
  Antonini JM ; Lin GX ; McKinney W ; Pathak D ; Sriram K
• Description:
  The potential for developing Parkinson's disease (PD)-like neurological dysfunction following occupational exposure to welding fumes (WF) is an emerging concern. Manganese (Mn) in welding consumables is suspected to cause the neurological deficits seen in welders. Indeed, we have shown that Mn-containing WF causes dopaminergic neurotoxicity in rats by provoking neuroinflammation, and reducing PD-related (PARK) proteins in the striatum and midbrain, areas typically affected in PD. Recent studies show that chronic exposure to low doses of Mn causes fine motor and cognitive impairment. Functional magnetic resonance imaging studies of welders reveals Mn accumulation and altered metabolites in cortical and thalamic regions, which correlated with reduced performance in fine motor, working memory, and executive function tasks. Such subclinical motor and non-motor dysfunction often precede clinical motor symptoms linked to dopaminergic neurodegeneration. These findings suggest that the neurological underpinnings in PD, manganism, and WF-mediated PD-like manifestation encompasses much more than degeneration of the nigrostriatal dopaminergic pathway and involves brain areas associated with sensorimotor, fine motor, and cognitive tasks, such as the cortex, thalamus, and cerebellum. Here, we examined the effects of WF on the frontal cortex (FCT, including pre-frontal cortex), parietal cortex (PCT, including motor cortex), and thalamus (THL, including subthalamic nucleus) of rats to determine if it instigates neurochemical and synaptic changes that are predictive of sensorimotor and cognitive impairment. Sprague-Dawley rats (male; 3 months old) were exposed by whole-body inhalation to fumes (4 - 6 mg/m3; 3 hours/day × 4 days/week × 5 weeks; for a total of 20 days) generated by gas metal arc-stainless steel (GMA-SS / WF), humanely euthanized at 1, 7, 28 or 112 days post-exposure, and brain areas collected. WF upregulated (1.4 to 1.7-fold) the mRNA transcripts for interferon-gamma (Ifng), inducible nitric oxide synthase (Nos2), matrix metalloproteinase 9 (Mmp9), dopamine D2 receptor (Drd2), and the solute carrier family 18 member A2 (Slc18a2 / Vmat2) in FCT after 1 d, suggestive of neuroinflammation and altered monoamine neurotransmitter signaling. Small decrements (10 - 20 %) in norepinephrine (NE) and serotonin (5-HT) were detected in the FCT at 7, 28, and 112 days. Reduced (22 - 30 %) NE, 5-HT, and dopamine (DA) was also seen in THL at 28 days, and the levels remained persistently lower at 112 days. Synaptophysin 1 protein increased (43 %), while ubiquitin C-terminal hydrolase L1 (UCHL1 / PARK5) protein levels decreased (44 %) in the FCT at 28 days. The FCT, primarily the prefrontal cortex, is known to coordinate and regulate cognitive tasks, including working memory, decision-making, attention, and learning. NE, DA, and 5-HT principally modulate this brain region, and dysregulation or imbalance in their levels affect neuronal circuits involved in cognitive processing. In conjunction, increased DRD2 expression is linked to poor cognitive performance. Together, our findings support the notion that a complex interplay of overlapping neural circuits, primarily involving nigrostriatal, cortical, thalamic, and cerebellar tracts are critical for eliciting key motor and non-motor symptoms in PD, and perhaps manganism, as well as welding-mediated PD-like manifestation. As dysregulation of corticothalamic region, linked to subclinical and non-motor symptoms, often precedes clinical motor signs, it may provide early insight into the neurodegenerative process. More research is necessary to identify biomarker signatures linked to sensorimotor and cognitive impairment that can aid early detection, intervention, and prevention of motor dysfunction associated with welding and Mn exposure. [Description provided by NIOSH]
• Subjects:
  Animals Nervous System Nervous System Diseases Occupational Health Respiratory System Safety Welding
• Keywords:
  Animal Studies Brain Matter Cognitive Function Inhalation Studies Neurological Disorders Neurotoxicology Parkinsons Disease Welding Fumes
• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  OSHA Region 3 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  192
• NIOSHTIC Number:
  nn:20067227
• Citation:
  Toxicologist 2023 Mar; 192(S1):462
• CAS Registry Number:
  Manganese (CAS RN 7439-96-5)
• Federal Fiscal Year:
  2023
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 62nd Annual Meeting & ToxExpo, March 19-23, 2023, Nashville, Tennessee
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:9b5c9dc2651cfd4ea3311601c34381a5850f81917ecc05d79fa676ab9d9f731b2d2c25a54ebcdc9a787c2935ad5de5f70f741eec07cf1c69ddcac27d3df6b750
• Download URL:
  https://stacks.cdc.gov/view/cdc/231352/cdc_231352_DS1.pdf
• File Type:
  [PDF - 1.11 MB ]