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

Abstract

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.

Peculiarities of the Molecular Structure and Functions of Metallothioneins in the Central Nervous System

“…Recently, Minami et al [44] found that induction of synthesis of MTs in the mouse brain after injections of thimerosal (ethyl mercury, a widespread mercury preservative used for preservation of vaccines) in small doses is structure-specific; moreover, this induction depends on the composition of injection mixture (with or without lipopolysaccharides) and on the duration of action of this agent. It was shown that the expression of mRNA of MT-I in the cerebellum and cortex increases, respectively, 6 and 9 h after injection of thimerosal (12 µg/kg); while the level of MT expression in the cerebellum is 3 times higher than that in the cortex.…”

Mercury exposure, nutritional deficiencies and metabolic disruptions may affect learning in children

“…The human subjects demonstrated a reduction in numerical zinc balance and an increase in numerical copper balance when they were fed fructose and HFCS compared to the adjustment period [ 9 ]. This finding along with the more recent finding of the historic use of mercury in high fructose corn syrup [ 55 ] is of particular significance today with respect to neurodevelopmental disorders since there is now evidence that autism can be caused by a biochemical abnormality that disables the metal clearing function of the zinc dependent metallothionein (MT) protein [ 61 - 64 ] and zinc deficiency plays a role in ADHD [ 10 , 11 ]. Two mechanisms with the potential for disabling MT functioning include severe zinc depletion [ 65 ] and toxic metal overload [ 61 - 64 ].…”

Oxidative enzymes in tissues of the catfish (Clarias gariepinus) exposed to varying levels of cadmium

“…Besides binding to Cd, MT is also an efficient interceptor of free radicals (Klaassen and Liu 1998). Available reports indicate that the brain has the capacity to induce the synthesis of MT (Aschner 1996;Minami et al 2010), although this molecule is not highly induced in the brain relative to other tissues. Thus, the induction of MT in the brain and distant tissues may partly account for the lack of significant change in the activities of brain oxidases on day 21.…”