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mTOR and the Cause of Autism

autism blocks

Autism is a hot topic, lets face it, the increase in prevalence has started to cause a panic in some people. That fear is what the anti-vaccination movement is hoping to capitalize on, but that doesn’t stop science from trying to solve what is really causing the problem. There are probably several roads to autism, most — if not all — of them genetic. Scientists have already found one definite genetic cause of autism and several genetic factors. Now it looks like they may have even found the actual brain changes that cause it. With these new discoveries come better testing, treatment and more individualized care.

Recent scientific studies have demonstrated how the brains of children with autism are hyper-connected in ways related to the severity in each individual. Unfortunately, the cause of this hyper-connectivity has eluded scientists.

Now, a new study extends the research in this area by revealing how children and teens with autism have a surplus of synapses — which are the points where neurons connect and communicate with each other — and this excess is due to a slowdown in the normal “pruning” process of brain development. This would help explain why children don’t present with autistic behaviors until a few years into development.

In mice, the drug rapamycin can restore normal synaptic pruning and improve autistic-like behaviors even when the drug is given after autistic behaviors appear. Though rapamycin has side effects rendering it unsafe for children, the drug still offers hope for a  starting point toward a treatment.

“The fact that we can see changes in behavior suggests that autism may still be treatable after a child is diagnosed, if we can find a better drug,” said Dr. David Sulzer, professor of neurobiology and senior author of the study.

“While people usually think of learning as requiring formation of new synapses, the removal of inappropriate synapses may be just as important,” Sulzer said.

In fact, our brains incorporate “pruning” — the horticultural practice of removing diseased and dead plants, or in this case synapses in the brain that are redundant or unused — into normal development. During infancy, a burst of synapse formation occurs, particularly in the cortex, a region linked to autistic behavior. The pruning which occurs in a normal brain eliminates about half of these cortical synapses by the late teen years.

To test the hypothesis that people with autism have more synapses than normal, the research team examined the brains of children with autism who had died from other causes. By comparison, 22 brains from children without autism were examined along with the 13 brains of children who died between ages 2 and 9, and the 13 brains of children who died between the ages of 13 and 20.

How did the researchers measure synapse density in the cortical region of each brain? With all our technology, they simply counted the number of tiny spines branching from each neuron; each spine connects with another neuron via a synapse. A low tech solution to a complex problem for sure, but still very effective.

By late childhood, the researchers discovered, spine density had dropped by about half in the normal brains, but only by about 16 percent in the autistic brains.

“It’s the first time that anyone has looked for, and seen, a lack of pruning during development of children with autism,” Sulzer said.

Clues to what might have caused defective pruning were also found. The autistic children’s brain cells were filled with old and damaged parts. In fact, they were deficient in a pathway known as “autophagy” (a term from the Greek meaning self-eating), a process by which cells perform their housekeeping work, or an easy way to think of it, the brain taking out the garbage. Following this discovery, the research team looked for more details as to what exactly had occurred in these autistic brains.

Using mouse models, the researchers traced the pruning defect to a single protein called mTOR. When mTOR is overactive, brain cells lose much of their “self-eating” ability. To test this and make sure they were on the right path, the researchers used rapamycin.

[Loony Hint: mTOR is a pathway that cells use to accomplish things. There are several pathways and I won’t go into detail since they can be very complex. The easiest way to explain it would be think of it as driving instructions, the end point being something the cells want to accomplish. The cells send a message which then follows a particular route in the cells (or pathway) to it’s end point. Hopefully that makes some sense.]

By administering rapamycin, a drug that inhibits the mTOR pathway, the researchers found they could restore normal autophagy and synaptic pruning — and even reverse autistic-like behaviors in the mice. Because large amounts of overactive mTOR were also found in almost all of the brains of the autism patients, the researchers believe the same processes may be occurring in children with autism.

“What’s remarkable about the findings is that hundreds of genes have been linked to autism, but almost all of our human subjects had overactive mTOR and decreased autophagy,” Sulzer said. “This says that many, perhaps the majority, of genes may converge onto this mTOR/autophagy pathway, the same way that many tributaries all lead into the Mississippi River.”

This means that while there have been several genes linked to autism, this might in fact be the cause, the one thing that all those genes affect. That isn’t just good news, this could very well be the news that the autistic community has been waiting to hear. Not only that, it offers a way in the future to detect autism before symptoms occur!

Personally, and this is just my belief, I think autism should be treated like deafness. Autistic children are brilliant just like the rest of us, they are just different. Just like deaf people aren’t stupid, they are just different, it’s what makes this world great. Just like the deaf community, the autistic community is diverse and unique. Sure having an autistic child can be scary, different is almost always scary. But that still doesn’t give people the right to prey on the scared and afraid.

I know it’s easy to want a simple explanation and a simple fix when you are scared, my advice is don’t lose hope. Sure this is just a baby step, but it’s a step toward an actual cure. This might actually be the cause of autism. It isn’t fear mongering and finger pointing, so as always with any autism post, suck it anti vaccination people.

Tang, G., Gudsnuk, K., Kuo, S., Cotrina, M., Rosoklija, G., Sosunov, A., Sonders, M., Kanter, E., Castagna, C., Yamamoto, A., Yue, Z., Arancio, O., Peterson, B., Champagne, F., Dwork, A., Goldman, J., & Sulzer, D. (2014). Loss of mTOR-Dependent Macroautophagy Causes Autistic-like Synaptic Pruning Deficits Neuron DOI: 10.1016/j.neuron.2014.07.040

2 responses

  1. khendradm

    Thank you for alerting us to this new study! Great to see more breakthroughs in autism research.


    August 25, 2014 at 12:11 pm

    • Thanks for the comment! I was really surprised by the study too, I’m glad you found it.


      August 25, 2014 at 2:42 pm

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