Autism-like social interaction deficits can be prevented in mice haploinsufficient for the sulfate transporter Slc13a4 by postnatal administration of N-acetylcysteine

Zhang Z1, Dawson P2, Simmons D1 and Piper M1

  1. The School of Biomedical Sciences, The University of Queensland.
  2. Mater Research Institute, The University of Queensland.

Mounting evidence suggests that dysregulated sulfate metabolism is associated with autism spectrum disorder (ASD). Here we reveal that the sulfate transporter SLC13A4 is a critical regulator of postnatal brain development, and that haploinsufficiency of Slc13a4 leads to deficits linked to ASD, including impaired social behaviours and altered neurogenesis. Importantly, conditional deletion of Slc13a4 demonstrates that the absence of this transporter during a critical postnatal period, but not afterwards, gives rise to the behavioural deficits. Excitingly, N-acetylcysteine, a safe, FDA-approved, amino acid derivative that can be metabolized to inorganic sulfate, rescues the ASD-like behavioural phenotypes when administered within this defined postnatal window. NAC may therefore have utility for the prevention of some forms of autism if administered in early life.