Methylmercury Pause
Study Suggests Long Latency for Neurotoxicity
Methylmercury (MeHg) easily crosses the
blood–brain barrier and accumulates in the central nervous system,
where it is demethylated to inorganic mercury. Chronic perinatal
exposure to environmentally relevant levels of MeHg is associated with
the occurrence later in childhood of neurobehavioral problems such as
impaired attention and fine motor function. Animal studies confirm this
association, but epidemiologic evidence is mixed despite extensive
study. Moreover, MeHg toxicity and the period of time before effects
appear are not completely understood, as few studies have been
conducted beyond the first months or years of life in either animals or
humans. Researchers now demonstrate in a mouse model that effects from
early exposure to methylmercury can occur years after early-life
mercury levels in the brain have declined
[
EHP 116:746–751; Yoshida et al.].
In the current study, investigators used two strains of mice—the
wild-type C57BL strain and the genetically manipulated metallothionein
(MT)-null strain. The latter was used to examine potential genetic
susceptibility to the toxic effects of MeHg exposure, as MT-null mice
do not produce metallothionein-I and II proteins that can bind metals
and protect against their toxic effects. Mice were exposed through diet
to low levels of MeHg (5 µg/g diet) from the first day of pregnancy
through the tenth day after birth. Offspring of the treated mice were
weaned at 28 days. At 12 and 52 weeks (roughly comparable to young
adulthood and middle age in humans), the offspring underwent behavioral
tests of their locomotor activity and learning ability. All animals
were weighed biweekly, and mercury concentrations in the brains,
livers, and kidneys were measured for 10-day-old mice and for the group
tested at 12 weeks.
In 10-day-old exposed mice, mercury
concentrations in the brain were 0.5 µg Hg/g body weight or lower, with
no significant differences observed between exposed wild-type mice and
MT-null mice. At 13 weeks, concentrations of mercury in the brain of
exposed groups were similar to those of the unexposed groups. Except
for one activity measure in female MT-null mice, exposure to MeHg did
not significantly affect behavioral test responses at 12 weeks. At 52
weeks, however, investigators observed significant effects in all
behavioral test responses, with MT-null mice being slightly more
affected. After 28 weeks, wild-type male and all MT-null mice exposed
to MeHg weighed significantly less than control mice, which may signal
an emerging toxic effect.
The authors demonstrate a long latency period
after perinatal exposure to low levels of MeHg and show that this
period may be influenced by genetic susceptibility, given the stronger
effect of MeHg exposure in MT-null mice. The existence of a latency
period suggests that a slow process, such as aging, plays a role in
MeHg toxicity, although the actual damage occurs much earlier in life.
Julia R. Barrett
originally published @ http://www.ehponline.org/docs/2008/116-6/ss.html#meth
