Mohawks and Autism- An unlikely connection
With how far science has come, eureka moments are becoming harder and harder to have. Most scientists will be lucky if they have one in their lifetime. So yes, rare, but then again, so is finding mice with a mohawk like hairstyle. As it turns out, both of these things happened just recently.
The connection came in a lab at NYU Langone Medical Center, months after an international team of neuroscientists bred hundreds of mice with a suspect genetic mutation tied to autism spectrum disorders.
Almost all the grown mice, had sideways,”over-groomed” hair with a highly stylized center hairline between their ears. Researchers knew it was a good sign they had found something — the telltale overgrooming [a repetitive motor behavior], had been linked in other experiments in mice to the brain condition that prevents children from developing normal social, behavioral, cognitive, and motor skills.
If you don’t know much about autism, people will typically exhibit noticeably dysfunctional behaviors, namely things like withdrawal and/or stereotypical, repetitive movements such as rocking. Now, for what may be the first time, an autistic motor behavior has been traced to specific biological pathways that are genetically determined.
Researchers knocked out a gene, [called Cntnap4] which affected two highly chemical messengers in the brain, GABA and dopamine. Both are neurotransmitters [which are just chemical signals released from one nerve cell to the next]. GABA, [short for gamma-aminobutyric acid] is the main inhibitory neurotransmitter in the brain. Dopamine is a well-known hormonal stimulant, highly touted for producing soothing, pleasing sensations. They typically get labelled [on the net at least] for having certain actions like the “love” hormone, but we will refrain from doing that here.
One of the key findings was that in the “Mohawk mice”, the reduced Cntnap4 production caused depressed GABA signaling and overstimulation of dopamine.This had an opposite effects on the neurotransmitters themselves because GABA is fast acting and quickly released, which meant changing it decreases signaling. On the other hand dopamine’s signaling is longer-acting; impairing its action increases its release [confusing I know].
“Our study tells us that to design better tools for treating a disease like autism, you have to get to the underlying genetic roots of its dysfunctional behaviors, whether it is overgrooming in mice or repetitive motor behaviors in humans,” says Dr. Fishell. “There have been many candidate genes implicated in contributing to autism, but animal and human studies to identify their action have so far not led to any therapies. Our research suggests that reversing the disease’s effects in signaling pathways like GABA and dopamine are potential treatment options.”
The U.S. Centers for Disease Control and Prevention [or CDC] estimate that right now one in 68 American children under age 8 has some form of autism. Five times as many boys are suffering from the spectrum of disorders when compared to girls. Keep in mind, the definition for autism was changed making it more wide reaching. This is part of the reason for the seemingly sudden increase in autistic children, this along with better diagnosing.
As part of the study, researchers performed dozens of genetic, behavioral, and neural tests with growing mice to isolate and pinpoint where Cntnap4 acted in their brains. They also tried to determine how it affected chemical signaling among specific interneuron brain cells, which help relay and filter chemical signals between neurons in localized areas of the brain.
They found that Cntnap4 in mature interneurons strengthened GABA signaling, but it did not have the same effect in younger interneurons. When researchers traced where Cntnap4 acted in immature brain cells, the tests showed that it stimulated, “a big bolus of dopamine.”
[Loony hint: a bolus just means a large amount at once, typically a lot larger than would be released on the average.]
So what’s next? The team plan further studies of how GABA and dopamine production changes as neurons mature. Specifically, they hope to determine what cellular mechanisms are involved in autism. The ultimate goal is to control and rebalance any biological systems that go awry. Hopefully one day soon offering a treatment for the disease.
And that, ladies and gentleman is why we don’t accept assertions [like the autism-vaccine connection]. We wouldn’t be that much closer to a cure for autism if science just accepted opinion or correlation. So suck it anti-vaccination people.
Already a neurologist? Well then you probably want the full study — here!
T.K., Fishell G., Tsien R.W., Peles E., Bourgeron T., Hoeffer C., Au E., Markx S., Kruglikov I. & Patel J.C. & (2014). Cntnap4 differentially contributes to GABAergic and dopaminergic synaptic transmission, Nature, DOI: 10.1038/nature13248