Sunday, February 23, 2014

Effect of Chloride and Oxytocin on Autism

News Brief by Lushna Mehra

Animal models have shown that high chloride levels at birth are potent indicators of autism spectrum disorder. Research Director at the Mediterranean Institute of Neurobiology Yehezkel Ben-Ari recently discovered that oxytocin, which is a hormone that causes labor, aids in controlling chloride levels at birth and, thus, in controlling the expression of autism. High chloride levels in the embryonic phase initially cause the neurotransmitter GABA to send excitatory signals that facilitate the creation of the brain, but later they cause GABA to act as an inhibitor that regulates and reduces chloride levels throughout adolescence and adulthood. Dr. Lemonnier and Ben-Ari’s teams conducted a clinical trial in 2012, hypothesizing that autistic patients had high chloride levels in their neurons. They were able to administer diuretics in order to reduce neuronal chloride levels. However, the team was unable to prove that children with autism had high neuronal chloride levels, so the treatment could not be entirely validated.

Currently, researchers incorporate two animal models of autism into their studies: a model dealing with a genetic mutation common in autism, and a model created by inserting sodium valproate, a known cause of birth abnormalities, into pregnant mice. The control mice did not seem to exhibit a decrease in neuronal chloride level from before to after birth; thus, the animal models failed to show that integral aspect of neuronal chloride levels at birth. In administering diuretics to the mother animals one day before delivery, however, there was a blatant decrease in neuronal chloride levels several weeks after that treatment during birth. This treatment is thought to have diverted any potential autistic behavior or brain activity in animals by adulthood.

The effect of oxytocin in the animal models appeared to have been akin to that of the diuretic in lowing neuronal chloride levels. In testing the effect of oxytocin in prenatal models, researchers injected a drug that blocks oxytocin into pregnant mice. They determined that the offspring were born with autism syndromes in terms of electrical and behavioral signs. Therefore, the team was able to conclude that oxytocin plays an essential role in decreasing chloride levels and was able to validate treatment via diuretics, which reduce chloride levels and control autistic expression. Ben-Ari insists that more information on the brain’s development as well as on the effect of genetic mutations and the environment that regulate the brain’s activity are essential for improved treatment of autism spectrum disorders.


Reference:
INSERM (Institut national de la santé et de la recherche médicale). "Autism: Birth hormone may control expression of the syndrome in animals." ScienceDaily. ScienceDaily, 6 February 2014.
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