A “Master Switch” for Synapses, Npas4
September 25, 2008 by Kristina Chew, PhD
Filed under Cause, Neuroscience
Scientists have previously posited that autism’s cause is at the synapse. Mutations in the genes for neuroligins—which ensure that signal transitions between nerve cells function—-have been suggested as a cause of autism. Neuroscientists at Children’s Hospital Boston have identified what is being called a “master switch” that organizes the functioning of inhibitory synapses. Synapses are the connections between brain cells and enable communication among neurons; they’re essentially for virtually all brain functions, such as memory, sensory perception, motor coordination, learning.
The “master switch” is Npas4, which is a transcription factor, a “switch” that activates or represses other genes; it regulates over 200 genes that play a role in “calming down” over-excited cells. From today’s Science Daily:
At birth, the rapidly developing brain teems with excitatory synapses, which tend to make nerve cells “fire” and stimulate their neighbors. But if the excitation isn’t eventually balanced, it can lead to epilepsy, and diseases like autism and schizophrenia have been associated with an imbalance of excitation and inhibition. The creation of inhibitory connections is also necessary to launch critical periods — windows of rapid learning during early childhood and adolescence, when the brain is very “plastic” and able to rewire itself.
Researchers bred mice that lacked Npas4; these mice appeared anxious and hyperactive as were also prone to seizures and neurological problems. Scientific American has more to say and also notes that findings such as these can be used to “identify people who are genetically at risk for neurological disorders and develop new drugs to prevent and treat them.”
Jeff Stimpson
Jill Cornfield
So if this is the case, what can be done about it?
I suspect that one thing would be to develop drugs to affect Npas4 function, and also emphasis on educational therapies that might “rewire” the brains of young children (something often said about intensive ABA).
When my son was seven he was taken for an MRI. The MRI showed a slightly smaller amygdala which is typical for autistic children. For severely autistic children it is swollen. I can’t see the Npas4 function as a cause of these symptoms. So I can only conclude it is another effect.
Theories about synapses and something interfering with synaptic connections have been very helpful, to me, in understanding why my son does some things.
*The MRI showed a slightly smaller amygdala which is typical for autistic children. For severely autistic children it is swollen.*
Ed, I always take those kinds of tests with a grain of salt now- my 3 kids are all over the spectrum, and generally the MRIs, CT, and PET scans that we’ve had over the years for studies have shown that they don’t even vaguely correspond to what’s accepted as “typical autism” scans. My one daughter who would appear “recovered” to anyone who doesn’t know her definitely has the most structurally abnormal brain in the house (abnormal as in not corresponding to typical brain structure, not abnormal as in bad), while my son who is still mainly non-verbal and has a host of other challenges has what appears to be a completely typical brain (more typical than mine, and I’m generally considered fairly functional if it’s not morning). My other daughter is kind of in the middle in terms of “autistic structure”, but she has other differences in her brain that should apparently be limiting her in ways that aren’t apparent at all.
While I think that all of these scans are worthwhile as they are contributing to our basic knowledge, and I think that this new study is extremely interesting, I think that a lot of the studies are meant to be seen as contributing to the general pool of knowledge rather than being applicable to each individual, if that makes any sense.
The synapse connections theory is useful to me as well- for a long time we’d been told that there was a chance that the prenatal steroids I’d been given to mature my kids’ lungs are they were likely to be very premature (triplets) had likely caused thinning of their myelin sheaths which interfered with synaptic connections. While I think that particular theory may have been debunked now, just watching my kids in action often leads me to think that there must be something that does interfere. They seem to get that “A-Ha! moment” after struggling to do a task or complete a thought much more so than other children do (at least when they were younger- now they rarely sit still long enough for me to see that moment). But again, that could just be something that I’m reading into their behaviour- I’m the first to admit that my interpretations may be completely wrong.
Synapse connectivity is found in most neurologically impaired people including adult stroke victims. Where there is a disruption of early brain development (ASD) or destruction of fully developed brain regions (stroke) strutural abnormalities will lead to synapse connectivity problems.
In autism MRI, PET and CA scans do not examine the brain microscopically. Autopsy reports over many decades have found a variety of stuctural abnormalities including a severe loss of cerebellar Purkinje cells, in the limbic system (amygdala and hippocampus) there are too many cells and they are too small, other structural abnormalities include cerebral cortex , brainstem and frontal lobes which is an indicator of a disruption of early brain development. None are specific to autism
http://www.ncbi.nlm.nih.gov/pubmed/17971078?
The synapse connectivity problems appear to be secondary to the abnormal brain structure. Treatment to ‘rewire’ synapse connectiviness for people with ASD’s and stroke are remarkeably similar, speech and language therapy, occupational therapy, physical therapy are all the most proven interventions for improving synapse connectivity.
http://www.npr.org/templates/story/story.php?storyId=94810949&ft=1&f=100
There much to be hopeful about in this area
Given the range of changes to the brain structure and the autopsies that showed issues with the Purkinje cells, I cannot see these changes being endogenous to the brain. The brain does not spontaneously combust (so to speak) just because it is autistic. What happens starts outside the brain.
Something got inherited in our family—one resemblance that’s definite between Charlie and Jim (with his ADHD) is a need for some extra “processing time” and often in matters involving language.
Kristina,
I do not doubt the genetics involved in autism. I also do not doubt that there is a genetic connection between ADHD and autism. Still, there is “something in the water”.
This is a problem for the pro-vax community. “Something in the water” and epidemic are such that if there is an epidemic then there is “something in the water”. That something has to meet the criteria of geography and the timing of the epidemic. Nothing meets that criteria like vaccines and the pro-vax community has nothing else to fill the vacuum that “It is not the vaccines” leaves. Therefore, no amount of proof by the medical community will be sufficient to quiet the feelings that vaccines and autism are linked. Note that none of what I have said so far proves that autism and vaccines are linked. I am just saying that the pro-vax arguments loose their punch without something to fill the vacuum. For me this is the reason that the argument that there is no epidemic is out there.
Now let’s suppose that the argument that there is no epidemic is true. There is no epidemic. The rate of autism never changed. It is all in the diagnostics. Logically, if the rate of autism never changes then it is logical to say that autism is genetic with no environmental cause or trigger. Now if autism rates never changed then there should be the same number of autistics in the previous generations as there are in this generation. So where are they? Autism is genetic. They have to be in the same families as the families that have autistic children. You can expect to have the same rate of autism among your siblings and your husband’s siblings as are in your family. Does that fit for you? Does it fit for other autistic families that you know?
Imagine if the same thing were said about AIDS. There would be outrage. Autism deserves the same reaction.
Jen,
Medically, all we have are effects, no cause is known.