Does X really mark the spot?
Why are there at least four boys diagnosed as autistic for every girl? This gender ratio is a big mystery in neuroscience, but holds clues to the causes of autism. Some of the genes associated with autism lie on the x chromosome and, early on, this alone was thought to be sufficient explanation for girls being less affected. This idea was reinforced by an autism-like syndrome that is part of a condition called Fragile X, in which a specific location on the x chromosome is particularly susceptible to damage.
Girls have two x chromosomes, whereas boys have one. We only need one operational x chromosome per cell. In fact, each cell in the body of a developing girl randomly deactivates one of the x’s, pushing it off to the side. This means that a mutation on one of the x chromosomes in girls only affects half of their cells, whereas the same mutation affects all the cells in boys. This is why x chromosome–linked disorders aren’t expressed as frequently, or as strongly, in women. The role of the x chromosome might still apply, but the story is far more interesting.
Activated microglia are strongly implicated in autism.
Autopsies of children diagnosed as autistic, but who died of unrelated causes, show evidence of inflammation and hyperactive microglia. These are our brain’s innate immune cells. Additionally, microglia have repeatedly been found to be abnormal in studies of animals rendered “autistic” through genetic and environmental manipulation. I discussed the role of microglia in brain development and vaccine injuries in a previous blog… but why might boys be more at risk?
Boys have more microglia than girls, but that’s not all.
Young male brains have more microglia than their female counterparts. These male microglia aren’t just more numerous… they are in a more activated state in certain brain regions during development, especially the first year of life. In other words, male brains are probably more susceptible to injury because their microglia are more numerous and active to begin with than those of girls. Why?
Activated microglia are now recognized as essential for shaping brain areas for male sexual behavior.
The brains of humans and other animals are sexually dimorphic, which means that men and women have differences in their brain wiring. Some brain regions are larger in males than females, whereas others are smaller. Many of these regional differences are linked with sexuality, parenting, and other gender-related behaviors.
The brains of male and female fetuses diverge during a process called “masculinization” of the brain. This occurs during early development in utero, and continues during the first year of life. Although we typically think of estradiol as a female hormone, brain masculinization is ironically under the influence of estradiol and estrogen receptors.
Estradiol is only present in male infants, because their testes secrete estradiol’s precursor, testosterone. The ovaries in female babies are hormonally quiet at this stage. Both neurons and glial cells respond to estradiol, changing density, shape, and even the number of neurons containing particular neurotransmitters.
Although estradiol induces the developing brain’s “masculinization,” the whole process requires an essential molecule called Prostaglandin E2 (PGE2). This is only secreted by microglia in an activated state. PGE2 is meant as a short-lived signaling molecule. By activating microglia artificially, we might be prolonging the brain’s exposure to PGE2.
The model for understanding autism proposed by Cambridge University Professor Simon Baron-Cohen describes it as the “extreme masculinized brain.” This doesn’t necessarily mean that male autistic individuals are anymore masculine than their peers… but does have implications for women. Professor Simon Baron-Cohen said: “One of our new findings is that females with autism show neuroanatomical “masculinization.”
Drugs given to animals to decrease their microglia activation lower PGE2 production. One unwanted consequence of taking these drugs for males was that their brain’s process of masculinization was stopped. Perhaps female brains naturally have fewer, and less active microglia, to prevent the masculinizing effects of PGE2.
Testes: double trouble for the developing male brain
Selenium deficiency used to be rare, but is increasingly more common because of our modern diet. Boys have an increased demand for selenium during development, because it is essential for both their brains and testes. Boys are, therefore, more susceptible to selenium deficiency than girls.
Selenium is a mineral that reduces some of the toxicity of aluminum, which is in vaccines as an adjuvant to increase immune reactivity. Selenium also protects body tissues against oxidative stress, helps the immune system defend against infection, and plays a role in modulating growth and development.
Selenium deficiency leads to more neuronal damage when in the presence of testosterone, and research has shown that the brains of male mice could be protected from this by castration.
Where do we go from here?
These findings suggest that we might be able to decrease the risk of vaccine injury if we took some simple measures. These would include screening boys for selenium deficiency, and treating them with a supplement or selenium rich food such as Brazil nuts and some fish. Another is checking levels of inflammatory markers known to activate microglia, and customizing vaccination protocols based upon the results of individuals. We also need to consider whether the timing of vaccination should be different for boys than girls. If there is a combined toxic effect of any nutritional deficiencies when brain development is undergoing major changes while testosterone is high (early infancy and onset of puberty), this suggests we should exercise caution at these ages.
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