Toxicant-Induced Reactive Gliosis in the Developing Nervous System

Details

• Personal Author:
  O'Callaghan JP
• Description:
  It is now widely accepted that astrogliosis represents a dominant response of the adult central nervous system to all types of injuries. This "reactive" state of the astrocyte can be induced by a diverse array of toxic substances as well as by neurological disease states and traumatic or ischemic injuries. Historically, astrogliosis was viewed as a permanent response involving cell division and scarring. We now are aware of the dynamic capacities of this neural cell type, including it's response to toxicant-induced injuries, i.e. time-dependent astrocytic hypertrophy, not hyperplasia. The reactive astrocyte, in vivo, can be monitored qualitatively and quantitatively by immunohistochemistry and immunoassay, respectively, of the astrocyte intermediate filament protein, GFAP. GFAP mRNA can now be reliably quantified, as well, using Taqman technology. The signaling mechanisms underlying the astroglial response to injury remain largely unknown but progress is being made through molecular analyses, e.g. by using inducible transgenic mice and the application of expression arrays to injury models. One area where the old dogma persists is in developmental neurotoxicology. The prevailing view remains that astrogliosis is diminished or absent in the developing nervous system. Despite this notion, we and others have used dose-, time- and region-dependent analysis of GFAP to show a robust astroglial response to diverse insults of the developing nervous system. These include early postnatal exposure to trimethyltin, triethyltin, cadmium, 6-OH dopamine, methamphetamine, NMDA, carbon monoxide, ethanol and bilirubin. Prenatal exposures tomethylazoxymethanol, methylmercury and ischemia also result in a postnatal increase in GFAP. All of these responses were target appropriate and suggest that, as in the adult nervous system, astrogliosis is a characteristic response to neural damage, regardless of the nature or the site of damage. Assessments of reactive gliosis should be incorporated into future developmental neurotoxicity testing paradigms. [Description provided by NIOSH]
• Subjects:
  Animals Cell Division Laboratories Nervous System Occupational Health Safety
• Keywords:
  Animal Studies Cell Division Central Nervous System Injuries In Vivo Studies Laboratory Animals Models Nervous System Neurological Diseases Neurotoxic Effects Neurotoxicity Neurotoxicology Neurotoxins Qualitative Analysis Quantitative Analysis Toxic Effects Traumatic Injuries

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• ISSN:
  0161-813X
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  Colorado ; OSHA Region 3 ; OSHA Region 8 ; 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:
  36
• Volume:
  22
• NIOSHTIC Number:
  nn:20021030
• Citation:
  Neurotoxicology 2000 Sep; 22:36
• CAS Registry Number:
  Cadmium (CAS RN 7440-43-9) ; Ethanol (CAS RN 64-17-5) ; Trimethylstannane (CAS RN 1631-73-8)
• Federal Fiscal Year:
  2000
• Peer Reviewed:
  False
• Source Full Name:
  Neurotoxicology. Proceedings of the 18th International Neurotoxicology Conference
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:b91ecf291f58def5acfe8af6e90950cbde43d779460486320e0db802e388b6d599ae88ad1705ed43d94e591221e6943db9bea2f5603f6ff060b0deb1aa51f2e9
• Download URL:
  https://stacks.cdc.gov/view/cdc/198611/cdc_198611_DS1.pdf
• File Type:
  [PDF - 40.53 KB ]