Glial Cells / Inflammation / Neuroinflammation / Oxidative Stress / Toxicants

Large Brains in Autism: The Challenge of Pervasive Abnormality

Excerpt: “Oxidative stress, brain inflammation, and microgliosis have been much documented in association with toxic exposures including various heavy metals…the awareness that the brain as well as medical conditions of children with autism may be conditioned by chronic biomedical abnormalities such as inflammation opens the possibility that meaningful biomedical interventions may be possible well past the window of maximal neuroplasticity in early childhood because the basis for assuming that all deficits can be attributed to fixed early developmental alterations in neural architecture has now been undermined.”

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  • June 29, 2016
Inflammation / Mercury / Neuroinflammation / Neuropeptides / Thimerosal / Toxicants

The levels of blood mercury and inflammatory-related neuropeptides in the serum are correlated in children with autism spectrum disorder

Excerpt:
“Levels of serum neurokinin A and BHg were measured in 84 children with ASD, aged between 3 and 10 years, and 84 healthy-matched children. There was a positive linear relationship between the Childhood Autism Rating Scale (CARS) and both serum neurokinin A and BHg. ASD children had significantly higher levels of serum neurokinin A than healthy controls (P < 0.001). Increased levels of serum neurokinin A and BHg were respectively found in 54.8 % and 42.9 % of the two groups. There was significant and positive linear relationship between levels of serum neurokinin A and BHg in children with moderate and severe ASD, but not in healthy control children. It was found that 78.3 % of the ASD patients with increased serum levels of neurokinin A had elevated BHg levels (P < 0.001). Neuroinflammation, with increased levels of neurokinin A, is seen in some children with ASD, and may be caused by elevated BHg levels. Further research is recommended to determine the pathogenic role of increased levels of serum neurokinin A and BHg in ASD. The therapeutic role of tachykinin receptor antagonists, a potential new class of anti-inflammatory medications, and Hg chelators, should also be studied in ASD."

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  • January 6, 2016
20 Papers / CDC / Glutamate / Glutathione / Mercury / Oxidative Stress / Review / Thimerosal / Toxicants

Mercury-Induced Toxicity: Multiple Mechanisms of Action

Excerpts:
“The difference in manifested toxicity of MeHg and EtHg are likely the result of the differences in exposure, metabolism, and elimination from the body, rather than differences in mechanisms of action between the two.”

“Summary and Conclusions

There are many commonalities/similarities in the mechanisms of toxic action of methylmercury and ethylmercury (from thimerosal)… Evidence for the similarity of the various mechanisms of toxicity include the following:

• Both MeHg and EtHg bind to the amino acid cysteine (Clarkson 1995; Wu et al. 2008)…

• Both decrease glutathione activity, thus providing less protection from the oxidative stress caused by MeHg and EtHg (Carocci et al. 2014; Ndountse and Chan (2008); Choi et al. 1996; Franco et al. 2006; Mori et al. 2007; Muller et al. 2001; Ndountse and Chan 2008; Wu et al. 2008)…

• Both disrupt glutamate homeostasis (Farina et al. 2003a, b; Manfroi et al. 2004; Mutkus et al. 2005; Yin et al. 2007).

• Both cause oxidative stress/creation of ROS (Dreiem and Seegal 2007; Garg and Chang 2006; Myhre et al. 2003; Sharpe et al. 2012; Yin et al. 2007)…

• Both cause effects on receptor binding/neurotransmitter release involving one or more transmitters (Basu et al. 2008; Coccini et al. 2000; Cooper et al. 2003; Fonfria et al. 2001; Ida-Eto et al. 2011; Ndountse and Chan 2008; Yuan and Atchison 2003).

• Both cause DNA damage or impair DNA synthesis (Burke et al. 2006; Sharpe et al. 2012; Wu et al. 2008).”

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  • January 1, 2016
GABA / Genes / Glutamate / Post-mortem

Reduced GABAergic Action in the Autistic Brain

Excerpt:
“Then, using magnetic resonance spectroscopy, we demonstrate a tight linkage between binocular rivalry dynamics in typical participants and both GABA and glutamate levels in the visual cortex. Finally, we show that the link between GABA and binocular rivalry dynamics is completely and specifically absent in autism.”

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  • December 16, 2015
Arsenic / CDC / Mercury / Toxicants

Autism spectrum disorder prevalence and proximity to industrial facilities releasing arsenic, lead or mercury

Abstract

Prenatal and perinatal exposures to air pollutants have been shown to adversely affect birth outcomes in offspring and may contribute to prevalence of autism spectrum disorder (ASD). For this ecologic study, we evaluated the association between ASD prevalence, at the census tract level, and proximity of tract centroids to the closest industrial facilities releasing arsenic, lead or mercury during the 1990s. We used 2000 to 2008 surveillance data from five sites of the Autism and Developmental Disabilities Monitoring (ADDM) network and 2000 census data to estimate prevalence. Multi-level negative binomial regression models were used to test associations between ASD prevalence and proximity to industrial facilities in existence from 1991 to 1999 according to the US Environmental Protection Agency Toxics Release Inventory (USEPA-TRI). Data for 2489 census tracts showed that after adjustment for demographic and socio-economic area-based characteristics, ASD prevalence was higher in census tracts located in the closest 10th percentile compared of distance to those in the furthest 50th percentile (adjusted RR=1.27, 95% CI: (1.00, 1.61), P=0.049). The findings observed in this study are suggestive of the association between urban residential proximity to industrial facilities emitting air pollutants and higher ASD prevalence.

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  • December 1, 2015
Aluminum / Cadmium / Mercury / Thimerosal / Zinc

Hair Heavy Metal And Essential Trace Element Concentration In Children With Autism Spectrum Disorder

Excerpt:
“The most deficient element was zinc (92% in target and 20% in control), then – manganese (55% and 8%) and selenium (38% and 4%). In case of cooper study revealed excess concentration of this element only in target group in 50% of cases. The contaminations to heavy metals were detected in case of lead (78% and 16), mercury (43% and 10%) and cadmium (38% and 8%). The study statistical results indicated, that deficient concentrations of trace elements such as zinc, manganese, molybdenum and selenium in hair significantly linked with ASD (Kramer’s V was 0,740; 0,537; 0,333; 0,417 accordingly). In case of cooper we got excess levels of this element and this data was highly linked with autism spectrum disorder. We got high associations and significant values between of lead, mercury and cadmium concentrations and ASD. Study results indicate that there are significant differences of hair essential trace elements concentrations in children with autism spectrum disorder comparing with healthy children group. The result obtained also showed high contamination to heavy metals such as lead, mercury and cadmium in ASD children compared to healthy ones. So, our study demonstrated alteration in levels of toxic heavy metals and essential trace elements in children with autistic spectrum disorders as compared to healthy children. This suggests a possible pathophysiological role of heavy metals and trace elements in the genesis of symptoms of autism spectrum disorders.”

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  • November 1, 2015
Genes / Human Fetal Cell Lines / MMR

Epidemiologic and Molecular Relationship Between Vaccine Manufacture and Autism Spectrum Disorder Prevalence

Excerpts:
“The average MMR coverage for the three countries fell below 90% after Dr. Wakefield’s infamous 1998 publication but started to recover slowly after 2001 until reaching over 90% coverage again by 2004. During the same time period, the average autism spectrum disorder prevalence in the United Kingdom, Norway and Sweden dropped substantially after birth year 1998 and gradually increased again after birth year 2000.”

“Conclusion: Vaccines manufactured in human fetal cell lines contain unacceptably high levels of fetal DNA fragment contaminants. The human genome naturally contains regions that are susceptible to double strand break formation and DNA insertional mutagenesis. The “Wakefield Scare” created a natural experiment that may demonstrate a causal relationship between fetal cell-line manufactured vaccines and ASD prevalence.”

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  • March 1, 2015
Androgens / Excitotoxicity / Glial Cells / Glutamate / Homocysteine / Immune / Inflammation / Mercury / Metallothionein / Mitochondria / Neurons / Review / Thimerosal / Toxicants / Transsulfuration

A possible central mechanism in autism spectrum disorders, part 2: immunoexcitotoxicity

Abstract

In this section, I explore the effects of mercury and inflammation on transsulfuration reactions, which can lead to elevations in androgens, and how this might relate to the male preponderance of autism spectrum disorders (ASD). It is known that mercury interferes with these biochemical reactions and that chronically elevated androgen levels also enhance the neurodevelopmental effects of excitotoxins. Both androgens and glutamate alter neuronal and glial calcium oscillations, which are known to regulate cell migration, maturation, and final brain cytoarchitectural structure. Studies have also shown high levels of DHEA and low levels of DHEA-S in ASD, which can result from both mercury toxicity and chronic inflammation. Chronic microglial activation appears to be a hallmark of ASD. Peripheral immune stimulation, mercury, and elevated levels of androgens can all stimulate microglial activation. Linked to both transsulfuration problems and chronic mercury toxicity are elevations in homocysteine levels in ASD patients. Homocysteine and especially its metabolic products are powerful excitotoxins. Intimately linked to elevations in DHEA, excitotoxicity and mercury toxicity are abnormalities in mitochondrial function. A number of studies have shown that reduced energy production by mitochondria greatly enhances excitotoxicity. Finally, I discuss the effects of chronic inflammation and elevated mercury levels on glutathione and metallothionein.

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  • January 1, 2015

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