After years of research that has focused on anything from environmental agents to viruses, scientists are starting to hone in on a much narrower line of research: that of the fetal and postnatal periods as possibly the most influential periods for the development of autism later on.

A team led by Yehezkel Ben-Ari of the INMED at the Mediterranean Institute of Neurobiology has apparently been able to make a breakthrough discovery that could lead doctors to treat children before and during birth in order to avoid the development of autism in childhood.

First of all, the team outlines in research published in the digest Science how high levels of chloride levels in the neurons of mice, used in laboratory trials that sought to achieve a recreation of a model of autism similar to that in man, which remained high after delivery or birth resulted in autism or autistic spectrum disorders. 


The research was done after scientists noticed that diuretic treatment on autistic children ameliorated the condition, and how in mice, when the same diuretic was employed, the mice who were then birthed had their condition corrected by the flushing of the chloride levels and developed normally.  
Another birth hormone, called oxytocin, when administered in mothers during delivery also help decrease the level of chloride during birth.  

At the basis of this discovery is the known fact that neurons are known to contain high levels of chloride during the child's life in utero. The high level of chloride in turn allow GABA, the chief chemical messenger in the brain to excite neurons, instead of inhibiting them, to facilitate construction of the brain.  However, once the child is delivered, that process needs to slow down, and it cannot if the levels of chloride do not subside.

A reduction in the level of chloride in the brain conversely allows GABA to inhibit nueron excitement, and that regulates the activity of the child's brain.  


This discovery followed the realization that conditions of the brain such as epilepsy, trauma etc, are usually present in concomitance with high levels of chloride.  That discovery led to the search for a possible connection to autism.  Ben Ari's team in 2012 then began administering diuretics to flush out chloride in children that had signs of autism and they noticed that the child's condition improved. 

The trial was done by creating a number of mice specimen with a gene variant called fragile X syndrome, a mutation that is believed to be most frequently associated with autism, and another group that was injected with sodium valproate a chemical substance known to cause brain abnormalities, such as austitic like conditions. 

What the researchers observed, was that in the autism model group, the chloride levels were very high resulting in great neuron excitement in the brain, which persisted in the animals druing their growth phase all the way to adulthood. 


The natural drop in chloride levels that is present in heathy individuals, was not seen in either of the two 'groups', the ones with the gene variant and the ones treated with valproate.

When the researchers administered a diuretic to the mother animal, in both groups, for 24 hours preceding delivery, the resulting drop in chloride levels reestablished a low level of the chemical that persisted even weeks after the birth of the trial specimens.  

What the scientists were able to observe therefore, was that the antenatal treatment of a single dose of diuretic restored brain activity to near normal levels and corrected the austistic behavior of the animal when it grew to adulthood. 

This research also lead to the study of oxytocin, a birth hormone that naturally lowers the levels of chloride in the child about to be delivered.  Oxytocin is a hormone that promotes labor, but it also has other effects, one of which is to reduce chloride, and an analgesic effect.  

When the researchers blocked oxytocin before birth, they observed that the offsprings had the entire autism like syndrome, both in the brain and in their behavior.  

This study obviously indicates that the solution to reducing or eliminating autism lies in prenatal observation - and therefore prevention - but also the observation of irregularities in delivery that can affect the levels of oxytocin and chloride.  


One important observation was that more study is necessary in the cases of caesarean deliveries that are pre-scheduled and not a result of resolving complications of natural birth, since they act before the natural process ensues and therefore disrupts the natural oxytocin process.  Although some believe that scheduled caesarians have increased the incidence of autism, these are controversial statements that need better understanding.  

Source : Science Daily/  1.7.14

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