The localization of mercury and metallothionein in the cerebellum of rats experimentally exposed to methylmercury

Abstract

Rats were dosed with methylmercuric chloride, either by gastric gavage (5 x 10 mg kg-1 body weight over a 15-day period), or in their drinking water (20 mg methylmercuric chloride l-1 for 14 or 42 days). Localization of mercury within the cerebellum was performed with a silver physical development technique, and metallothionein with dinitrophenyl hapten-sandwich immunohistochemistry. Mercury was detected in structurally undamaged Purkinje neurones and adjacent Bergmann glial cells; no mercury was detected in granule cells even though these small cells nearest the Purkinje layer had a high incidence of pyknotic nuclei. In general, metallothionein was detected mainly in Bergmann glial cells, Purkinje cells, astrocytes and glial cells of white matter; no metallothionein was detected in granule cells. We hypothesized that the resistance of Purkinje cells to methylmercuric chloride reflects their ability to transform organic mercurials to inorganic mercury that, in turn, induces the synthesis of radical-scavenging metallothionein molecules.

Methylmercury-Induced Increase of Intracellular Ca2+ Increases Spontaneous Synaptic Current Frequency in Rat Cerebellar Slices

“…Likewise, GABA-evoked currents in cerebellar granule cells in culture also seem to be much more sensitive to block by MeHg than are currents mediated by voltage-gated K ϩ channels or inwardly rectifying K ϩ channels. As noted above, cerebellar granule cells are more sensitive to MeHg-induced cytotoxicity than are Purkinje cells in vivo (Leyshon-Borland et al, 1994) and in vitro (Edwards et al, 2005) and sIPSCs in granule cells are 2ϫ to 3ϫ more sensitive to block by MeHg than are those in Purkinje cells (Yuan and Atchison, 2003). However, in many cases, after sIPSCs in granule cells were blocked completely, washing with MeHg-free solution containing 1 mM D-penicillamine, a MeHg chelator, completely restored the sIPSCs to preMeHg treatment level, whereas recovery was not seen in Purkinje cells (Yuan and Atchison, 2003).…”

Induction of metallothionein in mouse cerebellum and cerebrum with low-dose thimerosal injection

“…In addition, Mukai (1972) observed that astroglial cells conveyed the mercury-protein complex into neurons using autoradiographic study after the administration of ethyl mercury-S-cysteine labeled with tritium; thus, it is thought that astrocytes are the first target against organic mercury. Leyshon-Sørland et al (1994) reported that mercury was detected in undamaged Purkinje neurons and adjacent Bergmann glial cells when methyl mercury was administered orally to rats over 14 days, and MT-1 and MT-2 were detected in Bergmann glial cells, Purkinje cells, astrocytes, and glial cells of white matter in the cerebellum. Moreover, the expression of MT-1 protects astrocytes against the cytotoxic effects of methyl mercury (Yao et al 1999(Yao et al , 2000, and Giralt et al (2001) observed that MT-1 mRNA and protein increase in the Purkinje, granular layers, and white matter tracts of the cerebellum of GFAP-IL3 mice.…”

Astrocyte Metallothioneins (MTs) and Their Neuroprotective Rolea

“…Indeed, wherever a MeHg compound has been identified in biological media, it has been complexed to —SH‐containing ligands. However, MeHg has been reported to weakly bind to MT compared with the inorganic species Hg 2+ or Cd, 83–85 and it remains to be established whether the binding of MeHg to MT is associated with the attenuated effects on RVD and taurine release.…”