cell biol

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Cell Biol Toxicol. 2009 Apr 9.

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

thimerosal injection.Minami T, Miyata E, Sakamoto Y, Yamazaki H, Ichida S.

Department of Life Sciences, School of Science & Engineering, Kinki University,

3-4-1 Kowakae, Higashi-osaka, Osaka, 577-8502, Japan,

Thimerosal, an ethyl mercury compound, is used worldwide as a vaccine

preservative. We previously observed that the mercury concentration in mouse

brains did not increase with the clinical dose of thimerosal injection, but the

concentration increased in the brain after the injection of thimerosal with

lipopolysaccharide, even if a low dose of thimerosal was administered.

Thimerosal may penetrate the brain, but is undetectable when a clinical dose of

thimerosal is injected; therefore, the induction of metallothionein (MT)

messenger RNA (mRNA) and protein was observed in the cerebellum and cerebrum of

mice after thimerosal injection, as MT is an inducible protein. MT-1 mRNA was

expressed at 6 and 9 h in both the cerebrum and cerebellum, but MT-1 mRNA

expression in the cerebellum was three times higher than that in the cerebrum

after the injection of 12 microg/kg thimerosal. MT-2 mRNA was not expressed

until 24 h in both organs. MT-3 mRNA was expressed in the cerebellum from 6 to

15 h after the injection, but not in the cerebrum until 24 h. MT-1 and MT-3

mRNAs were expressed in the cerebellum in a dose-dependent manner. Furthermore,

MT-1 protein was detected from 6 to 72 h in the cerebellum after 12 microg/kg of

thimerosal was injected and peaked at 10 h. MT-2 was detected in the cerebellum

only at 10 h. In the cerebrum, little MT-1 protein was detected at 10 and 24 h,

and there were no peaks of MT-2 protein in the cerebrum. In conclusion, MT-1 and

MT-3 mRNAs but not MT-2 mRNA are easily expressed in the cerebellum rather than

in the cerebrum by the injection of low-dose thimerosal. It is thought that the

cerebellum is a sensitive organ against thimerosal. As a result of the present

findings, in combination with the brain pathology observed in patients diagnosed

with autism, the present study helps to support the possible biological

plausibility for how low-dose exposure to mercury from thimerosal-containing

vaccines may be associated with autism.