Toxicology of Industrial Compounds

248 NEUROTOXICITY TESTING OF INDUSTRIAL COMPOUNDS
cortex and hippocampus, while in regions such as hypothalamus and
cerebellum this process occurred entirely neonatally. It should be kept in
mind that in the rat also neuronal maturation and differentiation are not
completed at birth and continue to a large extent postnatally.
Exposure of pregnant rats to Aroclor 1254 did lead to a number of
alterations in GFAP levels in various brain regions in offspring as compared
to control animals. The most striking differences were observed in brain
stem. While in control animals of both sexes GFAP levels increased
postnatally, the normal developmental increase in perinatally exposed
animals was absent (Figure 18.3, upper panel). At 3 months the relative
deficit in GFAP levels was 41 per cent for male and 30 per cent for female
progeny. Already at the lowest dose of Aroclor 1254 (5 mg/kg) a maximum
decrease was observed (Figure 18.3, upper panel). In addition to brain stem,
a similar effect on GFAP levels was found in striatum although the relative
deficit at 3 months was somewhat less. Quite an opposite pattern emerged
in brain regions such as cerebellum, lateral olfactory tract and prefrontal
cortex, where GFAP levels were increased relative to unexposed progeny.
In hippocampus no significant changes in GFAP levels were encountered.
The question arose whether the observed neurodevelopmental toxicity in
rats by PCBs was specific for astroglial cells or also involved neuronal
maturation, differentiation and death. For this purpose the same nervous
tissues were used for quantitative assessment of a neuronal marker in the
form of synaptophysin. In brains of untreated adult control rats, regionspecific
differences were observed in synaptophysin concentrations, being
high in the prefrontal cortex, striatum and hippocampus and relatively low
in lateral olfactory tract, cerebellum and brain stem. Synaptogenesis for the
brain as a whole largely takes place in the rat from birth until postnatal
day 70 (Knaus et al., 1986). Regional differences in the speed of postnatal
synaptogenesis from 3 weeks to 3 months were found in a number of
structures being most pronounced in cerebellum (190 per cent increase) and
prefrontal cortex (170 per cent increase) while in brain stem little change was
observed.
As a result of perinatal exposure to Aroclor 1254, altered expression of
synaptophysin was observed. In most brain structures examined, including
brainstem (Figure 18.3, lower panel) significant decreases in synaptophysin
concentrations were found. This suggests that during development of the
central nervous system, PCBs may interfere with the formation of synaptic
vesicles, synaptogenesis, or formation of nerve terminals.
A straightforward interpretation of the present results is not possible at
this stage. However, what is clear is that perinatal exposure to PCBs may
cause changes in the structural composition of the central nervous system
both in the neuronal and the glial cell compartment. Apparently there are
different effects on nerve cells of the CNS depending on the brain region
involved. The brain stem and striatum are regions with decreased