• Home
  • Search Results
  • Oxytocin-mediated GABA inhibition during delivery attenuates autism pathogenesis in rodent offspring.

Oxytocin-mediated GABA inhibition during delivery attenuates autism pathogenesis in rodent offspring.

Science (New York, N.Y.) (2014-02-08)
Roman Tyzio, Romain Nardou, Diana C Ferrari, Timur Tsintsadze, Amene Shahrokhi, Sanaz Eftekhari, Ilgam Khalilov, Vera Tsintsadze, Corinne Brouchoud, Genevieve Chazal, Eric Lemonnier, Natalia Lozovaya, Nail Burnashev, Yehezkel Ben-Ari
ABSTRACT

We report that the oxytocin-mediated neuroprotective γ-aminobutyric acid (GABA) excitatory-inhibitory shift during delivery is abolished in the valproate and fragile X rodent models of autism. During delivery and subsequently, hippocampal neurons in these models have elevated intracellular chloride levels, increased excitatory GABA, enhanced glutamatergic activity, and elevated gamma oscillations. Maternal pretreatment with bumetanide restored in offspring control electrophysiological and behavioral phenotypes. Conversely, blocking oxytocin signaling in naïve mothers produced offspring having electrophysiological and behavioral autistic-like features. Our results suggest a chronic deficient chloride regulation in these rodent models of autism and stress the importance of oxytocin-mediated GABAergic inhibition during the delivery process. Our data validate the amelioration observed with bumetanide and oxytocin and point to common pathways in a drug-induced and a genetic rodent model of autism.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
γ-Aminobutyric acid, ≥99%
Supelco
Valproic acid, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
Oxytocin
Sigma-Aldrich
Oxytocin acetate salt hydrate, ≥97% (HPLC)
Sigma-Aldrich
Bumetanide, ≥98%
Sigma-Aldrich
Oxytocin, lyophilized powder, ~15 IU/mg solid (Prepared from synthetic oxytocin)
Sigma-Aldrich
γ-Aminobutyric acid, BioXtra, ≥99%
Oxytocin, European Pharmacopoeia (EP) Reference Standard
Supelco
Valproic acid solution, 1.0 mg/mL in methanol, ampule of 1 mL, certified reference material, Cerilliant®
Sigma-Aldrich
2-Propylpentanoic acid