Home > Science > Big brains and ROS—a new link emerges from the study of baby neurons

Big brains and ROS—a new link emerges from the study of baby neurons

A recent paper published in Cell Stem Cell reminds us that things are not always as they seem in biology.  Autism Speaks’ funded projects led by co-authors Dr. Harley Kornblum and Dr. Janel Le Belle revealed that reactive oxygen species (ROS)—the cellular culprits creating oxidative stress—are actually necessary and present at higher levels early in the lives of brain cells.

Reactive oxygen species are a byproduct of normal cell metabolism. They can be damaging due to their chemically unstable nature.  Peroxides are examples of ROS that result from the normal energy-production processes that take place inside the mitochondria in each cell.  Typically, cells have a host of enzymes and cellular antioxidants to defend against an accumulation of ROS.  However, environmental stressors such as ultraviolet radiation or overexposure to toxins can create more ROS than can be managed by an adult brain cell.

The research team was able to observe how young neurons not only used ROS to signal changes in cell processes, but needed more as they grew from neural stem cells into new neurons in the developing animal or human.  Previously, it was believed that stem cells maintained low levels of ROS to protect the cells from damage, but neural stem cells seem to actually need higher levels of ROS to go on and make new neurons.

Certainly this is not the first time ROS has been shown to create positive effects.  Previous research has shown that ROS can trigger the release of defense mechanisms against pathogens and initiate wound repair. However, more often, the build-up of ROS in cells is linked with cognitive decline in aging animals, when cellular mechanisms are less effective at removing ROS.

Other recent research has shown that by deleting genes that protect against a substantial increase in ROS, the young cells grow too much or “hyperproliferate”.  The result is early brain overgrowth, much like has been reported for young children with autism. We don’t yet know at what stage in human fetal development higher levels of ROS would lead to larger brains, but this is one of many next stages of study in this line of questioning.  From the studies in this report, it seems that the conversion of neural stem cells to differentiated neurons requires increased ROS, and suppressing it by various means also suppresses the creation of the new neurons from their stem cell predecessors.

Although the details of the “when” are as yet unknown with respect to early brain overgrowth due to increased ROS, the “how” is better understood.  The pathway that leads to overgrowth is part of the well-studied PTEN pathway.  We know a good bit about the molecular cascades in this pathway because the single gene mutations responsible for Tuberous Sclerosis complex (TSC)—one of the single gene disorders with a high proportion of individuals presenting with autism.  PTEN acts as a suppressor of a pathway that encourages growth and the proliferation of new cells.  Interestingly, Dr. Kornblum and his team showed that when ROS levels are reduced in developing brains, this pathway is less active and fewer new neurons are produced.  Too much ROS leads to hyperproliferation and too little reduces the number of new cells produced.

This new research underscores the important role of ROS in the developing brain; however it is not yet clear whether antioxidant therapy would be beneficial or harmful during normal development or even in the fetuses at higher risk for autism.  However, this is something that Dr. Kornblum and his team hope to explore, saying “The key here is that we cannot think of antioxidants as either universally good or universally bad.”


Janel E. Le Belle, Nicolas M. Orozco, Andres A. Paucar, Jonathan P. Saxe, Jack Mottahedeh, April D. Pyle, Hong Wu, and Harley I. Kornblum. (2011) Cell Stem Cell. Proliferative Neural Stem Cells Have High Endogenous ROS Levels that Regulate Self-Renewal and Neurogenesis in a PI3K/Akt-Dependant Manner. 8: 59–71. DOI 10.1016/j.stem.2010.11.028

  1. Noreen
    February 11, 2011 at 12:14 pm

    I feel they already know when this brain overgrowth happens. My child was a boy who had vaccine reactions. I also believe his brain was inflammed by them. They make it impossible to prove (though we do have stem cells banked before they shot him up with toxins). Even a little bit of toxin in the brain can do a lot of damage. Also, I saw a study that showed at 6 months (when I noticed my son have a sensory freak out, loose eye control and started shortly afterward loosing muscle tone and right leg turned in). These were very apparent. It so happens that he came down with Regressive Autism. Had skills then after shots…started to lose them. What is so hard to swallow about that? The US would have to clean up there Vaccine Act and provide help (humane) services for these kids. I think BOTH are possible. Autism has different routes, this one we can IMPROVE the LIVES OF MILLIONS. Get off the POT!

  2. Mackenzie
    February 11, 2011 at 6:13 pm

    Noreen~I’m with ya! My son lost the light in his eyes after his flu vaccine @ 10months and regressed worse and worse after every other required vaccination thereafter but yet I was FORCED to do so in order to put him in daycare so we could work!?! It sickens me that our government, who we trust to protect us, are harming our children DAILY!!! :( Anyway, I work with a wonderful developmental pediatrician now was was the 1st and only Doc to ever agree with the toxicity link and she has since put him on many vitamins to the point where he is detoxing his body independently (no scary chelation~only stinky pee) plus he’s on the GFCF diet! Best wishes to you and your family…

  3. Sarah
    February 12, 2011 at 12:35 pm

    This is exciting research (I have a head overgrowth kid – who also happens to be a multiple regression kid).

  4. Katie Wright
    February 14, 2011 at 4:15 pm

    I also feel like we already know why brain overgrowth happens.
    Most regressive kids exhibit head growth right after the fevers, the infections and the febrile seizures, at least mine did.
    This obsession w/ fetal development and ASD has come at the expense of post natal environmental research- so under funded. Don’t these doctors get it- our kids were not born with autism.
    The brain overgrowth is not complicated. What is complicated is treating it and our kids need in the here and now. Our children need so much help.
    I find it depressing that such massive amounts of money have been spent on research that will not help children and/or is telling us what we already know.
    “We cannot think of antioxidants are good or bad.” That’s it, that is the insight?

    These doctors need to catch up with our families. Who among us does not run a pharmacy of supplements in their home. CoQ10, MethB12 shots, GABA, 5HTP, carintine, taurine, vit D, and on and on and on and yes an antioxidant.

  5. Carrie Elsass
    February 16, 2011 at 4:36 pm

    My son was born with his head circumference in the 25th percentile, but by the end of the first year, it was up around 100%, despite height & weight remaining right in the average range. Are there any particular “suspects” as to which vaccine(s), adjuvants or other ingredients might be most culpable in this type of inflammation?If he got any mercury at all, it would have been in the first HepB delivered in the hospital…but the head growth seems to have started after the DPT shots began.
    Despite this rapid head growth, he was well and meeting milestones until the MMR and varicella were given at 13 months- within 2 weeks he became ill and had multiple infections and wonky immune system as shown by labs for years. I would really like to know more about any theories or research that has been done or is being done in terms of the head growth issue.

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