Mercury - Toxicology of Metals - page 696

In the mouse, the fi rst morphological changes
observed by Berthoud et al . (1976) were in the corpus
striatum, above all the putamen, thalamus, and
hypothalamus. These authors observed no changes
in the cerebellum. MacDonald and Harbison (1977)
who used another strain of mice reported fi rst
changes in the cerebellum and no other degenerative
changes in the CNS. None of these authors reported
on investigations of peripheral nerves (Berthoud
et al ., 1976; MacDonald and Harbison, 1977). The
discrepancy between these observations can possi-
bly be explained by genetic differences among the
mouse strains. Jacobs et al . (1977) and Carmichael
et al . (1975) studied the effects of MeHg on the CNS
of the rabbit. They found, similar to what has been
seen in the rat, that the fi rst morphological changes
appeared in the dorsal root ganglia, but at increasing
doses degenerative changes in the rabbit appeared in
small neurons and in granular cells of the cerebellum
and of the parietal and occipital parts of the cortex.
In the cat, the fi rst morphological changes are seen
in the cerebellum with degeneration of the granu-
lar cells, fi rst in the vermis and at higher doses in
the deep part of the cortical sulci. Purkinje cells also
show degeneration. At still higher doses, changes
appear in the occipital, parietal, and temporal cortex
(Charbonneau et al ., 1974; Grant, 1973). The toxicity
of MeHg has also been studied in the pig in which no
changes were seen in the cerebellum (Davies et al .,
1976; Tryphonas and Nielsen, 1973). The neurotoxic
effects in the dog are similar to those in the pig. The
fi rst changes appear in the brain cortex with the most
pronounced ones in the visual cortex. No changes
are seen in the cerebellum or other parts of the CNS
or peripheral nerves (Miller, E. et al ., 1972; Mozai,
1975).
The extensive studies performed on primates show
consistently that the primary injury is located in the
cerebral cortex, especially in the visual cortex and other
cortical sensory centers. Changes in the cerebellum or
the peripheral nerves have been observed at moderate
toxic doses in marmosets (Eto et al ., 2002). The changes
in the occipital cortex in primates appear at a concen-
tration of MeHg in the brain of 5-10

discussion of the neuropathological fi ndings of MeHg
poisoning is found in Shiraki (1979).
The aforementioned studies at the cellular level,
involving in vitro cultures and in vivo systems,
illustrate that MeHg is primarily toxic for the cells of
the brain, neurons, and glia cells, and the compound
seems to interfere with membrane function and struc-
ture, protein, and macromolecule synthesis. On this
basis it could be expected that in all species, MeHg
causes a consistent type of injury involving a large
part of the nervous system. However, this is not the
case. The injury found is very differentiated and spe-
cifi c and involves mainly sensory and cortical areas
in some species and basal ganglias in others. In some
species, the cerebellar cortex is involved and in oth-
ers it is not. In affected cortical areas, some neurons
are injured and others are not. This pattern is diffi cult
to explain unless transport of MeHg by the interneu-
ronal axonal fl ow in an anterograde direction is pos-
tulated. This assumption could explain why sensory
centra of the brain are fi rst affected. In these centra,
afferent paths converge, and, as a consequence, the
MeHg concentrations increase continuously with
each synaptic step.
Motor centers are protected because the paths are
efferent, and MeHg taken up in the system is trans-
ported peripherally out of the motor nuclei. This
hypothesis can also explain the long latency between
maximal mercury load in the body and the appear-
ance of signs seen in man and mammals, because
the axonal fl ow is relatively slow. The fi nding that
toxic doses of MeHg are accumulated in subcortical
association pathways (Berlin et al ., 1975a) and the
fact that in MeHg-poisoned monkeys, degeneration
of the axons of the large efferent motor bundles in
the spinal cord is observed (Berlin et al ., unpublished
data) both support this hypothesis. The hypothesis
can also explain the observed species differences. It
is reasonable to assume that in different species, dif-
ferent nerve paths and centra are dominant, depend-
ing on the function of the species. In primates, visual
centra have a very dominating position in the brain.
It has been shown that MeHg at low concentrations
inhibits polymerization of tubulin to microtubuli.
These observations offer a possible cellular mecha-
nism that can explain the neural damage, because the
microtubuli are likely to have a central function in
axonal transport, especially in the anterograde direc-
tion. In tissue cultures (Choi et al ., 1981b), as well as
in the brain cortex of Squirrel monkeys (Berlin et al .,
unpublished data), the primary injury seems to be in
the periphery of the neuron at the end of the neu-
rite, the axon, or the dendrite. The available infor-
mation concerning the effect of MeHg on the axonal

µ g/g (Berlin et al .,

1975b; Shiraki, 1979).
Accumulation of MeHg in the brain occurs in the
fetal brain, in the growing and maturing brain as well
as in the adult brain, and gives rise to neuronal dam-
age that is especially located in the cortical sensory
centra. The mechanism of this injury is still unknown;
thus, it is still unclear whether the primary injury is
inhibition of membrane function or whether vital proc-
esses in the cell nucleus are interfered with. There are
research results supporting both possibilities. A further