Toxicology of Industrial Compounds

250 NEUROTOXICITY TESTING OF INDUSTRIAL COMPOUNDS
Table 18.1 Cerebral calcium accumulation
a Systemic dose.
b Intrastriatal dose.
synaptophysin and increased GFAP in structures such as cerebellum, lateral
olfactory tract, and prefrontal cortex. Such a situation could arise when
neurons in these latter regions fail to receive proper input from developing
neurons originating in brain stem and striatum. Further investigations into
this interesting topic may provide further clues for the developmental
toxicity of PCBs and related compounds that possibly could aid in the
interpretation of neurobehavioural effects, for instance altered sexual
behaviour and reproduction (Smits-van Prooije et al., 1993).
The findings observed in cerebellum are consistent with a phase of
hypothyroidism during development but it is clear that a conclusive role
for thyroid hormone remains to be further established. The present results
furthermore suggest that alterations in synaptophysin/GFAP levels may be
useful and sensitive parameters to study compounds suspected of
developmental neurotoxicity.
Conclusion
The results with various neurotoxins demonstrate that assessment of
gliotypic proteins such as GFAP may be a useful tool to identify and
quantify persistent toxic insults of the CNS, especially when this is backed
up by indications for loss of neuronal elements, e.g. decreased
synaptophysin concentration. Also in circumstances of developmental
neurotoxicity, caused by chemicals such as PCBs, an approach based on
changes of gliotypic and neurotypic proteins may provide a promising
biomarker. Of course, further investigations with various other compounds
are required to substantiate these interesting findings.
Cerebral calcium accumulation may be useful as an early indicator of
neurotoxicity on a more prospective basis as is suggested by various
examples of neurotoxic compounds (summarized in Table 18.1). Because in
unlesioned brain regions the background levels of calcium uptake remain