The role of metallothionein (MT) in the brain in heavy metal detoxification
is relatively unexplored. Brain copper (Cu) elevation although unusual in
chronic Cu poisoning in sheep, has been shown to occur after treatment with
the chelating agent ammonium tetrathiomolybdate (TTM). The aim of this stu
dy was to investigate the expression of MT in TTM Cu-enhanced sheep brains,
with immunohistochemical techniques. Brains from TTM-treated, Cu-poisoned
sheep were examined for MT immunolabelling with a mouse monoclonal antibody
(E9) for MT1 and MT2, and compared with brains from untreated sheep. Brain
samples were analysed separately for Cu and zinc (Zn) by atomic absorption
spectrophotometry. Markedly increased MT immunoreactivity was found in ast
rocytes of the cerebellum, thalamus/hypothalamus, cerebrum and medulla oblo
ngata of the high-Cu brains, corresponding to the regional Cu elevations. M
T immunolabelling was also found in the pia mater, choroid plexus and epend
ymal cells. Neurons were rarely labelled. MT induction within astrocytes an
d at the blood-brain barrier suggests that these are sites of stabilization
and possibly transport for Cu and supports the hypothesis that the astrocy
te compartment modulates metal homeostasis, conferring protection on vulner
able neurons and effecting damage limitation. (C) 1999 W.B. Saunders Compan
y Limited.