Friday, May 23, 2014

Autism and Ionizing Radiation


Diagnoses of autism are increasing and more researchers are concluding that environmental causes are contributing in significant ways to the rising diagnoses. Environmental injuries that are suspected to play a role in autism include DNA damage, primarily in the form of de novo mutations, epigenetic changes in how genes encode proteins, and endocrine system disturbances. The environmental culprits potentially responsible for these injuries are varied. This mini-essay seeks to redress a limitation in the autism research on environmental insults by exploring the potential role of radioisotopes, such as strontium and radiocesium, in contributing to rising rates of autism.
Autism has long known to have a genetic component but the research so far has failed to identify alleles increasing risk that are replicable across large populations (with the exception of Fragile X syndrome). Instead, the genetic pattern revealed by new high-resolution genomic microarray genomic analysis is that people with autism have a statistically significant increase in de novo copy number mutations as compared to parental and sibling controls (Sebat et al 2007). Research data suggest mutations found at higher rates among people with autism are micro-deletions affecting genes likely to code for, or regulation expression of, the structure and function of brain synapses, mitochondria, and oxytocin (Sebat et al., 2007; Smith, Spence, & Flodman, 2009).
The increased rate of de novo mutations among people with autism suggests the condition may be environmentally-mediated and/or caused (Kinney et al., 2010). Environmental insults could create harmful de-novo mutations, which could cause autism directly by impacting mitochondrial DNA and/or DNA encoding neurons. Environmental insults could also create epigenetic damage, altering how genes encode proteins (see for discussion Hertz-Picciotto, Croen, Hansen, Jones, van de Water, and Pessag, 2006). For this reason, Herbert et al. (2006) have called for further research on autism and environmental genomics.
Environmentally caused genetic or epigenetic damages could also increase susceptibility to additional insults, thereby contributing to autism indirectly. Reduced capacity to combat oxidative stress, for example, has previously been proposed as one mechanism for autism (James, et al, 2006 ).  Damage to genes encoding for antioxidants could increase vulnerability to a wide array of contaminants, including complex chemicals (such as pesticides and herbicides), heavy metals (e.g., lead and mercury), and radioisotopes (such as radioiodine, radiocesium, strontium, etc.). Damage to genes encoding for glutathione suggest one specific pathway for genetically or epigenetically conferred susceptibility since glutathione is the most powerful antioxidant in the brain and low-levels of intracellular glutathione have been found in many children with autism (Theoharides et al., 2012).
The role of the environment, particularly the role of “insults,” has recently been recently been documented for a number of conditions, including ADHD and cognitive decline, and is suspected with autism (Herbert et al., 2006; Hertz-Picciotto et al., 2006; Kinney et al., 2009). Environmental insults can alter the regulatory functions of DNA and break DNA strands.  De Novo mutations caused by environmental insults can affect development and be transmitted across generations. Indeed, advanced paternal age has recently been linked with autism through the intergenerational transmission of de novo mutations (Kong et al., 2012).
In sum, people with autism are more likely to have de novo DNA mutations that either cause autism directly or increase susceptibilities through complex gene interactions and/or by exacerbating susceptibilities to other insults. Research is ongoing to identify likely environmental insults in autism and other neurological condition. Research has focused on the role of stable elements that are proliferating in the environment, such as lead and mercury, as well as agricultural and industrial pollutants (see for example, Hertz-Picciotto, Croen, Hansen, Jones, van de Water, and Pessag, 2006). Other researchers have proposed a role for increases of low-frequency magnetic radiation on autism rates (Herbert & Sage, 2012).
So, far however, relatively few studies of autism and other neurological conditions have focused on exposure to radioisotopes, such as strontium, radioiodine and radiocesium, which are byproducts of the atmospheric testing and the atomic age, including industrial accidents and routine nuclear energy operations. This can be considered a deficit in the existing literature given evidence that radiation exposure increase the frequency of DNA strand breaks in mitochondria and across the genome more generally in the form of “increased instability of repeat-DNA sequences” in descendants of affected individuals. (Dubrova, Plumb, Guiterrez, Bolton, and Jeffreys, 2000).
Although the relationship between autism and ionizing radiation has not been explored, studies have found other neurological developmental effects believed to be derived from Chernobyl fallout. One study concluded that that chronic low-dose exposure to radiation from Chernobyl caused increased rates of neural tube-defects and conjoined twins: (Wertelecki, 2010). A study of populations impacted by fallout in Sweden found more subtle neurological effects. Almond, Edlund and Palme found cognitive effects, particularly retardation among children exposed in utero at 8 to 25 weeks of gestation.  The critical period for neuorogenesis rougly correspond to this time period.
Nowakowski and Hayes (2008) explore the myriad effects of radiation on early brain development (i.e., neurogenesis), which include double-strand breaks of DNA impacting cell proliferation and migration during critical periods of early brain development. They conclude that early fetal development is particularly susceptible to effects of relatively low levels of exposure to radioisotopes from nuclear accidents, among other sources of exposure. Research on autism suggests that important brain injuries are most likely to occur during early neurological development and infancy.
Nuclear fallout of radioisotopes enters the food and water cycles so there are multiple vectors for human exposure. Radioisotopes can be inhaled or ingested with water and food. Some radioisotopes, such as tritium, can penetrate the skin. The human body regards radioisotopes such as radiocesium and radioiodine as analogs of potassium and stable iodine so radioisotopes may be taken up on the blood stream. Some radioisotopes can penetrate the blood-brain barrier. Strontium and cesium can be absorbed into the brain’s calcium ion channels. For example, Xu-Friedman and Regehr (1999) fond that strontium impacts Purkinje cell synapses in mouse cerebellar slices. Strontium entered presynaptic terminals.


REFERENCES 

M. A. Xu-Friedman and W. G. Regehr (1999) Presynaptic strontium dynamics and synaptic transmission Biophys J. 1999 April; 76(4): 2029–2042. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1300177/
Abstract
Strontium can replace calcium in triggering neurotransmitter release, although peak release is reduced and the duration of release is prolonged. Strontium has therefore become useful in probing release, but its mechanism of action is not well understood. Here we study the action of strontium at the granule cell to Purkinje cell synapse in mouse cerebellar slices. Presynaptic residual strontium levels were monitored with fluorescent indicators, which all responded to strontium (fura-2, calcium orange, fura-2FF, magnesium green, and mag-fura-5). When calcium was replaced by equimolar concentrations of strontium in the external bath, strontium and calcium both entered presynaptic terminals. Contaminating calcium was eliminated by including EGTA in the extracellular bath, or by loading parallel fibers with EGTA, enabling the actions of strontium to be studied in isolation. After a single stimulus, strontium reached higher peak free levels than did calcium (approximately 1.7 times greater), and decayed more slowly (half-decay time 189 ms for strontium and 32 ms for calcium). These differences in calcium and strontium dynamics are likely a consequence of greater strontium permeability through calcium channels, lower affinity of the endogenous buffer for strontium, and less efficient extrusion of strontium. Measurements of presynaptic divalent levels help to explain properties of release evoked by strontium. Parallel fiber synaptic currents triggered by strontium are smaller in amplitude and longer in duration than those triggered by calcium. In both calcium and strontium, release consists of two components, one more steeply dependent on divalent levels than the other. Strontium drives both components less effectively than does calcium, suggesting that the affinities of the sensors involved in both phases of release are lower for strontium than for calcium. Thus, the larger and slower strontium transients account for the prominent slow component of release triggered by strontium.


Almond, D., Edlund, L., Palme, M.  (2009, January) Chernobyl’s subclinical legacy: prenatal exposure to radioactive fallout and school outcomes in Sweden, http://people.su.se/~palme/QJErevisionJan23_09.pdf
Bowers, K., Bressler, J., Avramopoulos, D., Newschaffer, C., & Fallin, D. (2011). Glutathione pathway gene variation and risk of autism spectrum disorders J Neurodevelopmental Disorders, 3(2): 132–143.
Dubrova, Yuri  E., Plumb, M., Gutierrez, B., Emma Boulton, E., & A. J. Jeffreys (2004, May 4). Genome Stability: Transgenerational mutation by radiation. Nature,  http://www.nature.com/nature/journal/v405/n6782/abs/405037a0.html
Herbert, M. R., Russo, J. P., Yang, S., Roohi, J., Blaxill, M., Kahler, S. G., Cremer, L., & E. Hatchwell. (2006). Autism and environmental genomics. NeuroToxicology, 27(5), 671-84, http://www.ncbi.nlm.nih.gov/pubmed/16644012.
Hertz-Picciotto, I., Crone, L. A., Hansen, R., Jones, C. R., van de Water, J., & I. N. Pessah (2006). The CHARGE Study: An epidemiological Investigation of Genetic and environmental factors contributing to autism. Environmental Health Perspectives, 114(7), 1119-1124.
James S.J., Melnyk, S., Jernigan, S., Cleves, M.A., Halsted, C. H., Wong D.H., et al. (2006). Metabolic endophenotype and related genotypes are associated with oxidative stress in children with autism. Am J Med Genet B Neuropsychiatr Genet., 141(8), 947–56.
Kinney, D. K., Barch, D. H., Chayka, B., Napoleon, S., Munir, K. M. (2010) Environmental risk factors for autism: Do they help cause do novo genetic mutations that contribute to the disorder? Medical Hypotheses, 74, 102-106.
Kong, A., M. L. Frigge, G. Masson, S. Besenbacher (2012) Rate of de novo mutations and the importance of father’s age to disease risk. Nature 488, 471–475 (23 August 2012) doi:10.1038/nature11396 Received 28 February 2012 Accepted 04 July 2012 Published online 22 August 2012 http://www.nature.com/nature/journal/v488/n7412/full/nature11396.html?WT.ec_id=NATURE-20120823
Nowakowski, R. S. & Hayes, N. L. (2008). Radiation, retardation and the developing brain: Time is the crucial variable. Acta Pediatrica, 97, 527-531.
Sebat J., Lakshmi, B., Malhotra, D., et al. (2007, April). Strong association of de novo copy number mutations with autism. Science, 316, 445–9.
Smith, M., Spence, M.A., Flodman, P. (2009) Nuclear and mitochondrial genome defects in autisms. Ann NY Acad Sci ., 1151, 102–32.
Wertelecki, W. (2010).  Malformations in a Chornobyl-impacted region. Pediatrics 125(4), e836-e843; published ahead of print March 22, 2010, doi:10.1542/peds.2009-2219.
 Xu-Friedman, M. A. & W. G. Regehr (1999) Presynaptic strontium dynamics and synaptic transmission Biophys J. 1999 April; 76(4): 2029–2042. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1300177/


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5 comments:

  1. Looking around over the years and doing some research here is my recommendations for producing healthy babies: be conceived and born in a rural area prior to nuclear testing . . . say before 1945. The advantage of the time period is that the food you eat will also be less likely to have toxins in it from herbicides and pesticides. Your clothing will be safer and made in the USA as will most things. You will even get a better education. No cell phones or Internet or porn. On the whole, that time or even earlier and especially in a rural area are the finest.

    Of course this presents a real problem for potential parents. But your children will never be pressured into psych meds. In rural areas there will be horses and plenty of common sense. Prejudice will unfortunately also exit in some abundance. But good water without fluoride and plenty of fresh air. And you may end up in an extended family or at least have relatives near by. The word stranger may have very little meaning for you until you leave for college.

    When I consider all the toxins, the PTSD which they now say enters into sperm and becomes incorporated into the psyche of the fetus (WWII, Korean and Vietnam Conflicts, Iraq . . .), the DU, the chem trails, the additives in all the packaged food, the many STD's
    . . . no wonder the DSM keeps growing with more and more mental illnesses . . . My favorite though not in there yet is CODD--that's compulsive obsessive diagnosing disorder which the people who write that text clearly suffer from!

    Yes, the prescription is fantastic and unrealizable but the point is this: Who alive in the 1950's as I was hearing over and over GE's Progress is our most important product" would ever have thought they meant this mess? Or Fukushima? Progress is neutral. A disease like Mers progresses to death about 1/3 of the time. Was that slogan prophetic but like Cassandra--not believed in its most relevant sense?

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  2. A very thorough case study, but what else do you expect from Majia, the heavyweight hitter in the Biosciences?

    Alas, although the Earth is a big place, and humans have suffered all sorts of indignities throughout their history, many of which we have sorted out (the invention of plumbing, hurrah! - for the lucky sectors of the global population, which does not yet include everyone), there does seem to be by any rational calculation an increasing number of assaults on the living organism. Ionizing radiation and nuclear fallout and pollution, chemtrails (whatever is in them, aluminum etc.), GMOs, food additives such as bovine growth hormones, antibiotics, plastic in fast food burgers, all sorts of unhealthy ingredients in processed foods, not to mention general environmental pollutants such as heavy metals from coal combustion or plastic bags floating around the ocean.

    The problem is that the modern scientific paradigm is reductionist in outlook, understandably in a sense, because how else do you get a grip on a problem unless you look at one of the parts to begin with. But there is not much effort devoted to looking at these parts holistically, otherwise you are laughed at by the "hard headed" scientists. Of course, holism also leads to metaphysical and spiritual aspects that scientists eschew like the plague having deemed themselves the ultimate arbiters of truth and reality.

    Richard Wilcox, "Reporting From Tokyo"
    http://wilcoxrb99.wordpress.com/

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  3. Hello, can we say vaccines?

    ReplyDelete
  4. Hi,
    It's rare for someone in the world of academia to get involved with outing the harms caused by the scientific elite, funded by the power elite's money, as they together pursue the eugenicist programme they began in earnest 150 years ago. Take some time to read the olivefarmercrete blog if you have time.

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