γ-aminobutyric acid (GABA) is a neurotransmitter of the central nervous system, namely a molecule that transmits nervous signals. During prenatal development GABA excites neurons, whereas at birth it has the opposite function and thus inhibits neuronal activity.
Yehezkel Ben-Ari, INSERM, France, and co-workers discovered that this switch in GABA signaling is abolished in animal models of autism, a disorder characterized by altered neuronal development and impaired social interactions. The researchers demonstrated that the defective GABA switch is associated with an abnormal concentration of chloride ions present in the neurons of autistic-like animals.
As the intracellular concentration of chloride ions can be pharmacologically controlled with the drug bumetanide, the researchers administered this compound to pregnant rodents one day before their delivery. This treatment restored normal concentrations of chloride ions in the neurons of the newborns. Consequently the offspring of bumetanide-treated mothers underwent the GABA switch and did not show autistic-like features.
These findings may open new therapeutic strategies for autism.
- Oxytocin-Mediated GABA Inhibition During Delivery Attenuates Autism Pathogenesis in Rodent Offspring,
R. Tyzio, R. Nardou, D. C. Ferrari, T. Tsintsadze, A. Shahrokhi, S. Eftekhari, I. Khalilov, V. Tsintsadze, C. Brouchoud, G. Chazal, E. Lemonnier, N. Lozovaya, N. Burnashev, Y. Ben-Ari,
Science 2014, 343, 675–679.