Biol. Pharm. Bull. 28(12) 2308—2311 (2005)

نویسندگان

  • Tatsumi ADACHI
  • Manabu KUNIMOTO
چکیده

major hazardous environmental pollutants. MeHg is easily absorbed from the intestine, and transported into the brain across the blood-brain barrier. It has been demonstrated that MeHg neurotoxicity may be modulated by dysfunction of astrocytes such as disturbing ion homeostasis and the uptake of glutamate [a major excitatory transmitter of the central nervous system (CNS)] in cultures, since glutamate can induce neuronal cell damage. Indeed, a recent study revealed that MK-801, an antagonist of N-methyl-D-aspartate receptor, reduced MeHg toxicity, particularly in the cerebral cortex but not in the cerebellum, suggesting the involvement of glutamate in in vivo MeHg neurotoxicity, at least in the cerebral cortex. Not only MeHg but also mercury vapor (Hg) absorbed from lung tissue is also taken up into the brain before it is oxidized, and then converted to Hg. Since Hg is not easily eliminated, the CNS is critically affected by repeated exposure to Hg vapor. Interestingly, both MeHg and Hg converted from MeHg accumulate preferentially in astrocytes rather than in neurons, whereas Hg is generally seen in neurons after exposure to mercuric chloride or Hg vapor. Since glutamate uptake in cultured astrocytes is also inhibited by Hg , an astrocyte dysfunction induced by Hg may also indirectly contribute MeHg neurotoxicity. MeHg neurotoxicity has been observed at relatively local regions including granule cells in the cerebellum and neurons in the interstices of the visual cortex. Although reasons for this are uncertain, it might be possible to reflect brain region-specific susceptibility to mercuric compounds in astrocytes. This assumption might be supported by the facts that there are brain region-dependent differences in glutamate uptake and regulations of its transporters in cultured astrocytes. However, few reports demonstrate the differences in the cytotoxic effects induced by mercuric compounds between the astrocytes from different brain regions. In the present study, astrocyte cultures prepared from the cerebral hemisphere and cerebellum of newborn rats were exposed to MeHg or Hg under several culture conditions, and changes in viable cell numbers and morphology were investigated as indicators of acute toxicity of mercuric compounds. We also examined the relationship between susceptibility and Hg accumulation after exposure to mercuric compounds in these cultured astrocytes.

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تاریخ انتشار 2005