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Serotonin 2A Receptor - 5-HT2AR

Effect of thimerosal on the neurodevelopment of premature rats.
Published: 2013
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

Chen YN, Wang J, Zhang J, Li SJ, He L, Shao DD, Du HY. World J Pediatr. 2013 Nov;9(4):356-60. doi: 10.1007/s12519-013-0443-z. Epub 2013 Nov 14.

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.”

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Serological association of measles virus and human herpesvirus-6 with brain autoantibodies in autism.
Published: 1998
SYNOPSIS

A high percentage of autistic children with positive antibodies to the measles and/or human herpesvirus-6 (HHV-6) also have autoantibodies to brain components. Might the MMR vaccine be an early event in brain autoimmunity?

CITATION

Singh VK, Lin SX, Yang VC. Clin Immunol Immunopathol. 1998 Oct;89(1):105-8.

SUMMARY

Environmental exposures to toxins as well as viral infections are known to be triggers for autoimmunity. Individuals with autism suffer from a variety of immunological abnormalities with 55-70% having autoantibodies to brain antigens that include myelin basic protein (MBP), neuron-axon filament proteins (NAFP), and serotonin receptor. Many parents have reported the onset of autism soon after receiving a vaccine for the measles-mumps-rubella (MMR) and/or diptheria-pertussis-tetanus (DPT). The authors point out that both measles virus and human herpesvirus-6 (HHV-6) can manifest neurologic sequelae, show molecular mimicry with MBP and NAFP, and are associated with demyelination. To understand a possible association of viruses to brain autoimmunity, these researchers investigated virus serology of the measles virus and HHV-6. Children diagnosed with autism using the DSM-IIIR criteria were compared to normal controls. Both the controls and the children with autism had a high percentage of positive titers to measles as well as HHV-6 antibodies. According to the authors this was to be expected given that, “A high proportion (78%) of general populations is known to have positive titers of HHV-6 antibody.” The high percentage of measles antibody titers (85%) in children with autism was also expected. There is a high rate of seroconversion post MMR vaccination and none of the children had a history of exposure to the wild-type measles infection. An interesting finding was revealed when comparing the virus serology to brain autoantibodies. Among the control group, there were no brain autoantibodies found in any participant. However, among autistic subjects:

“approximately 90% of measles-IgG-positive sera also had anti-MBP”

“73% of measles-IgG- positive sera also had anti-NAFP”

“84% of HHV-6-IgG-positive sera also had anti-MBP”

“72% of HHV-6-IgG-positive sera also had anti-NAFP.”

“the higher the virus antibody titer the greater the chance of brain autoantibody”

The report closing by stating, “In conclusion, we suggest that while the etiology is not known, it is quite instructive to consider environmental factors, for example measles virus and HHV-6, as etiological agents linked to autoimmunity in autism.”

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