Nature explains the unusual effects that chloride ions can have on our developing brains, and what that means for a drug that seems to help autistic kids socialize:
The findings, reported today in Science, do not suggest that autism spectrum disorders can be prevented in children. But researchers not involved in the study say that they add support to a controversial clinical trial suggesting that some children with autism benefited from taking a common diuretic medication called bumetanide.
In that trial, a team led by neuroscientist Yehezkel Ben-Ari at the Mediterranean Institute of Neurobiology in Marseille gave 60 children bumetanide or a placebo daily for three months. Children who had less severe forms of autism showed mild improvements in social behaviour after taking the drug, and almost no adverse side effects were observed.
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Studies in humans and animals have suggested that GABA, which in healthy people typically inhibits the activity in neurons, is altered in autism and instead activates some brain cells. Ben-Ari’s team hypothesized that the system malfunctions at around the time of birth, when GABA-releasing neurons in the developing brain switch from activating neurons to inhibiting them. A drop in the concentration of chloride ions in neurons makes this switch. Thus, bumetanide, which reduces the levels of chloride in cells, might restore inhibitory GABA function and improve autism symptoms.
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The researchers discovered that, in both models, neurons in a brain area called the hippocampus remained excitatory after birth in response to GABA and contained higher levels of chloride than those in normal rodents.
These problems, however, were reversed when the rodent mothers were given bumetanide one day before giving birth. Their pups also displayed fewer autistic-like behaviours: for example, both rats and mice produced vocalizations more typical of normal rodents.