Insulin receptor sensitization restores neocortical excitation/inhibition balance in a mouse model of autism.
Fu-Sun Lo, Reha S Erzurumlu
PMID 29484150WHAT IT FOUND
In mouse brain slices from an autism-related Met mutation, insulin plus pioglitazone increased inhibitory signals and shifted the balance toward inhibition, while insulin alone did not.
Key findings
01In wild-type slices, insulin reduced the AMPA/GABA ratio to 0.79 ± 0.07, and insulin plus pioglitazone produced 0.74 ± 0.03.
02In Met-Emx1 slices, insulin alone left the AMPA/GABA ratio at 3.53 ± 0.42, while insulin plus pioglitazone reduced it to 0.69 ± 0.08.
03In Met-Emx1 slices, insulin plus pioglitazone increased spontaneous inhibitory current amplitude to 17.44 ± 0.55 pA, but this remained smaller than the 20.22 ± 0.56 pA seen in wild-type slices with the same treatment.
STILL TO COME
How it was doneWhat they found
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What it does not show
The study was done in mouse brain slices, not in people, so it does not show what pioglitazone would do in a patient with autism. Only 5 mutant mice and 5 control mice were used, and the electrophysiology results come from slice preparations rather than behaving animals. The reported rescue used insulin plus pioglitazone, not pioglitazone alone, so the contribution of pioglitazone alone cannot be separated. The conclusion that this relates to children with autism sensory hypersensitivity is a proposed mechanism, not a tested clinical result. The Discussion admits the mechanism by which Met deficiency alters insulin receptor desensitization is unknown.
Declared interests
The supplied text states funding by the National Institutes of Health and gives no other conflicts declaration.
The easy way to misread this
Do not read this as evidence that pioglitazone improves autism symptoms in patients. The effect was measured in mouse brain slices, and the rescue used insulin plus pioglitazone, not pioglitazone alone.