Carbon Nanotube Exposure Triggers a Cerebral Peptidomic Response: Barrier Compromise, Neuroinflammation and a Hyperexcited State

Details

• Personal Author:
  Bishop L ; Campen MJ ; Erdely A ; Mostovenko E ; Muldoon PP ; Ottens AK ; Saunders S
• Description:
  The unique physicochemical properties of carbon nanomaterials and their ever-growing utilization generate a serious concern for occupational risk. Pulmonary exposure to these nanoparticles induces local and systemic inflammation, cardiovascular dysfunction, and even cognitive deficits. While multiple routes of extrapulmonary toxicity have been proposed, the mechanism for and manner of neurologic effects remain minimally understood. Here, we examine the cerebral spinal fluid (CSF)-derived peptidomic fraction as a reflection of neuropathological alterations induced by pulmonary carbon nanomaterial exposure. Male C57BL/6 mice were exposed to 10 or 40 microg of multi-walled carbon nanotubes (MWCNT) by oropharyngeal aspiration. Serum and cerebrospinal fluids were collected 4 h post-exposure. An enriched peptide fraction of both biofluids was analyzed using ion mobility-enabled data-independent mass spectrometry for label-free quantification. MWCNT exposure induced a prominent peptidomic response in the blood and CSF; however, correlation between fluids was limited. Instead, we determined that a MWCNT-induced peptidomic shift occurred specific to the CSF with 292 significant responses found that were not in serum. Identified MWCNT-responsive peptides depicted a mechanism involving aberrant fibrinolysis (fibrinopeptide A), blood-brain barrier permeation (homeobox protein A4), neuroinflammation (transmembrane protein 131L) with reactivity by astrocytes and microglia, and a pro-degradative (signal transducing adapter molecule, phosphoglycerate kinase), anti-plastic (AF4/FMR2 family member 1, vacuolar protein sorting-associated protein 18) state with the excitation-inhibition balance shifted to a hyperexcited (microtubule-associated protein 1B) phenotype. Overall, the significant pathologic changes observed were consistent with early neurodegenerative disease and were diagnostically reflected in the CSF peptidome. [Description provided by NIOSH]
• Subjects:
  Animals Cardiovascular Diseases Cardiovascular System Chemistry Environmental Exposure Laboratories Lung Diseases Nervous System Occupational Health Respiratory Tract Diseases Risk Assessment Risk Factors Safety

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• Keywords:
  Author Keywords: Nanoparticles Blood Brain Barrier Carbon Carbon Nanotubes Cardiovascular System Disorders Cerebrospinal Fluid Chemical Properties Cognitive Function Excitotoxicity Exposure Levels Health Effects Laboratory Animals Mass Spectrometry Multi-walled Carbon Nanotubes MWCNT Nanomaterials Nanoparticles Nanotechnology Neurodegenerative Disease Neuroinflammation Neurological System Neuropathology Neurotoxicity Peptidome Peptidomics Proteins Pulmonary System Disorders Risk Factors

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• ISSN:
  1096-6080
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  New Mexico ; OSHA Region 3 ; OSHA Region 6 ; Virginia ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  107-119
• Volume:
  182
• Issue:
  1
• NIOSHTIC Number:
  nn:20062664
• Citation:
  Toxicol Sci 2021 Jul; 182(1):107-119
• Contact Point Address:
  Andrew K. Ottens, Department of Anatomy and Neurobiology, Virginia Commonwealth University, PO Box 980709, Richmond, VA 23298-0709
• Email:
  akottens@vcu.edu
• CAS Registry Number:
  Carbon (CAS RN 7440-44-0) ; Carbon nanotubes (CAS RN 308068-56-6)
• Federal Fiscal Year:
  2021
• NORA Priority Area:
  Manufacturing
• Performing Organization:
  University of New Mexico Health Sciences Center, Albuquerque, New Mexico
• Peer Reviewed:
  True
• Start Date:
  20130901
• Source Full Name:
  Toxicological Sciences
• End Date:
  20150831
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:4655bfe5aaa79734d9046b13365c0613f31b88eb1184c608189b30578cc934a409bb6f6fd004c2fa6a92b1a9d6f4e9c62f9f948eb44efb5bf8b427205a9778f3
• Download URL:
  https://stacks.cdc.gov/view/cdc/225862/cdc_225862_DS1.pdf
• File Type:
  [PDF - 870.32 KB ]