TY - JOUR
T1 - Immunocytochemical detection of metallothionein (MT1 and MT2) in copper-enhanced sheep brains
AU - Dincer, Z.
AU - Haywood, S.
AU - Jasani, B.
PY - 1999/1
Y1 - 1999/1
N2 - 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 study 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 astrocytes of the cerebellum. thalamus/hypothalamus, cerebrum and medulla oblongata of the high-Cu brains, corresponding to the regional Cu elevations. MT immunolabelling was also found in the pia mater, choroid plexus and ependymal cells. Neurons were rarely labelled. MT induction within astrocytes and at the blood-brain barrier suggests that these are sites of stabilization and possibly transport for Cu and supports the hypothesis that the astrocyte compartment modulates metal homeostasis, conferring protection on vulnerable neurons and effecting damage limitation.
AB - 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 study 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 astrocytes of the cerebellum. thalamus/hypothalamus, cerebrum and medulla oblongata of the high-Cu brains, corresponding to the regional Cu elevations. MT immunolabelling was also found in the pia mater, choroid plexus and ependymal cells. Neurons were rarely labelled. MT induction within astrocytes and at the blood-brain barrier suggests that these are sites of stabilization and possibly transport for Cu and supports the hypothesis that the astrocyte compartment modulates metal homeostasis, conferring protection on vulnerable neurons and effecting damage limitation.
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U2 - 10.1053/jcpa.1998.0254
DO - 10.1053/jcpa.1998.0254
M3 - Article
C2 - 10098014
AN - SCOPUS:0032896266
VL - 120
SP - 29
EP - 37
JO - Journal of Comparative Pathology
JF - Journal of Comparative Pathology
SN - 0021-9975
IS - 1
ER -