Excitatory currents are increased at birth in the Shank3 mouse model of autism

What is it about?

Autism spectrum disorders which are induced by both genetic and environmental factors result from an imbalance between excitation and inhibition in the brain. However, no common hallmark has been found until now. In our previous research, we showed that the activity of the GABA neurotransmitter at birth is affected in 2 models of autism. Moreover, restoring this activity attenuates the autistic symptoms, suggesting that GABA activity at birth is a hallmark of autism. To validate this hypothesis, we used a genetic mouse model of autism where the Shank3 gene is mutated. As we didn’t find any changes in GABA activity at birth, we conclude that this pattern cannot be considered a general hallmark of autism. However, an imbalance between excitation and inhibition in favor of excitation was already present at birth.

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Why is it important?

The prevalence of autism spectrum disorders (ASD) has continuously increased over past years, but treatment remains limited as of today. In order to improve therapeutic approaches, understanding the mechanisms underlying this pathology is necessary. ASD are already known to result from an imbalance between excitation and inhibition but favor for one over the other is dependent on the brain area studied. Hypothesizing that an alteration of GABA activity at birth may be a more robust mechanistic defect and testing it is crucial to improve our therapeutic possibilities. Even though our hypothesis was not confirmed, the observation that this pattern of activity can not be defined as a general hallmark of ASD may explain why clinical treatments like bumetanide administration do not ameliorate the deficits present in all children with ASD. Nonetheless, the enhancement of excitatory activity already at birth is important as little is known about early life development, although ASD is defined as a neurodevelopmental disorder.

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