Dopamine D4 Receptor - DRD4
Effect of thimerosal on the neurodevelopment of premature rats.
SYNOPSIS
An animal model of early life exposure to thimerosal finds it adversely impacts learning and memory and may be associated with the development of autism in susceptible individuals.
CITATION
SUMMARY
Thimerosal is a preservative used in vaccines and contains approximately 49% mercury. This animal model study was undertaken to investigate the neurodevelopmental effect of exposure to thimerosal in premature rats. Four groups of premature rats received four different doses of thimerosal (32.8, 65.6, 98.4 or 131.2 μg/kg) injected into the gluteus maximus on postnatal day 1. A fifth group served as a control and received a saline injection. Tests were performed 44-48 days post injection to determine spatial learning and memory function. On day 49 the animals were euthanized and prepared for immunohistochemical staining to determine the expression of the dopamine D4 receptor (DRD4), serotonin 2A receptor (5-HT2AR) and apoptosis (programmed cell death) in the prefrontal cortex. The DRD4 receptor is associated with memory function while the 5-HT2AR receptor correlates with episodic memory. Previous rat studies have demonstrated that early life exposure to thimerosal alters the dopamine and serotonin systems. Similarly, this study found a significant decrease in the expression of DRD4, 5-HT2AR and learning at the highest dose of thimerosal. The decrease in receptor expression correlated with increased levels of apoptosis. In all but the lowest exposure group, memory function was significantly decreased when compare to the control group. The authors close by saying, “In conclusion, our results are consistent with previous studies in mice, rats, rhesus macaques, and humans, demonstrate that exposure to mercury from thimerosal- containing vaccines in susceptible populations, such as premature infants, may be associated with neurodevelopmental disorders like autism.”
Activation of methionine synthase by insulin-like growth factor-1 and dopamine: a target for neurodevelopmental toxins and thimerosal
SYNOPSIS
Scientists identify vaccine mercury’s role in blocking crucial neurodevelopmental pathways.
CITATION
M Waly, H Olteanu, R Banerjee, S-W Choi, JB Mason, BS Parker, S Sukumar, S Shim,
A Sharma, JM Benzecry, V-A Power-Charnitsky and RC Deth. Molecular Psychiatry , (2004) 9, 358–370.
SUMMARY
“The ethylmercury-containing preservative thimerosal inhibited both IGF-1- and dopamine-stimulated methylation with an IC50 of 1nM and eliminated MS activity. Our findings outline a novel growth factor signaling pathway that regulates MS activity and thereby modulates methylation reactions, including DNA methylation. The potent inhibition of this pathway by ethanol, lead, mercury, aluminum and thimerosal suggest that it may be an important target of neurodevelopmental toxins.”