Effect of toluene inhalation on astrocytes and neurotrophic factor in rat brain

Forensic Sci Int. 2000 Sep 11;113(1-3):233-8. doi: 10.1016/s0379-0738(00)00215-2.


Toluene, an abused substance in Japan, is a neurotoxic chemical that has been shown to have neurobehavioral and electrophysiological effects. In previous work, both acute and chronic effects of toluene on cells have been studied extensively. However, although glial cells are thought to play an important role in the survival of neurons in the brain, the effect of toluene on glial cell function has not yet been characterized. To elucidate this, the effect of toluene inhalation on astrocytes in rat brain was examined. Toluene exposure (1500 ppm for 4 h on 4-10 days) augmented glial fibrillary acidic protein (GFAP) immunoreactivity, particularly in the hippocampus and cerebellum. Quantitative analysis showed that toluene inhalation markedly enhanced GFAP expression in the hippocampus and cerebellum. In both regions, proliferating cell nuclear antigen (PCNA) showed no obvious changes, but glutamine synthetase (GS)-immunoreactive cells were markedly increased by toluene exposure. Thus, the elevation of GFAP expression was induced by astrocyte activation rather than by cell proliferation. If toluene exposure activates astrocytes, astrocytes may play a role in the neurophysiological changes observed in toluene intoxication. A neurotrophic factor, basic fibroblast growth factor (b-FGF) was observed immunohistochemically in the capillary vessel walls in the hippocampus and the cerebellum of toluene-intoxicated rats. Basic-FGF may have induced GFAP expression both in the hippocampus and the cerebellum. So, other neurotrophic factors may affect the difference of GFAP elevation between the hippocampus and the cerebellum. These differences may relate to neurobehavioral function of each brain part after toluene exposure.

MeSH terms

  • Acute Disease
  • Animals
  • Astrocytes / drug effects*
  • Brain / drug effects*
  • Brain Chemistry / drug effects*
  • Chronic Disease
  • Disease Models, Animal
  • Glial Fibrillary Acidic Protein / analysis
  • Glial Fibrillary Acidic Protein / drug effects
  • Glutamate-Ammonia Ligase / analysis
  • Glutamate-Ammonia Ligase / drug effects
  • Immunohistochemistry
  • Inhalation Exposure / adverse effects*
  • Male
  • Nerve Growth Factors / analysis*
  • Nerve Growth Factors / drug effects*
  • Proliferating Cell Nuclear Antigen / analysis
  • Proliferating Cell Nuclear Antigen / drug effects
  • Rats
  • Rats, Wistar
  • Substance-Related Disorders / complications*
  • Substance-Related Disorders / pathology*
  • Time Factors
  • Toluene / poisoning*


  • Glial Fibrillary Acidic Protein
  • Nerve Growth Factors
  • Proliferating Cell Nuclear Antigen
  • Toluene
  • Glutamate-Ammonia Ligase