title: Oxytocin-mediated GABA inhibition during delivery attenuates autism pathogenesis in rodent offspring.
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.
authors: Mediterranean Institute of Neurobiology (INMED), U901, INSERM, Marseille, France.
authors: Roman
authors: R
authors: Tyzio
authors: Romain
authors: R
authors: Nardou
authors: Diana C
authors: DC
authors: Ferrari
authors: Timur
authors: T
authors: Tsintsadze
authors: Amene
authors: A
authors: Shahrokhi
authors: Sanaz
authors: S
authors: Eftekhari
authors: Ilgam
authors: I
authors: Khalilov
authors: Vera
authors: V
authors: Tsintsadze
authors: Corinne
authors: C
authors: Brouchoud
authors: Genevieve
authors: G
authors: Chazal
authors: Eric
authors: E
authors: Lemonnier
authors: Natalia
authors: N
authors: Lozovaya
authors: Nail
authors: N
authors: Burnashev
authors: Yehezkel
authors: Y
authors: Ben-Ari
mesh_terms: D000818:Animals; D001321:Autistic Disorder / Q000139:chemically induced* / Q000235:genetics* / Q000378:metabolism; D001522:Behavior, Animal; D002034:Bumetanide / Q000008:administration & dosage; D002712:Chlorides / Q000378:metabolism; D019610:Cytoprotection; D004195:Disease Models, Animal; D005260:Female; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics; D008431:Maternal-Fetal Exchange; D051379:Mice; D010121:Oxytocin / Q000378:metabolism*; D036801:Parturition; D011247:Pregnancy; D051381:Rats; D014635:Valproic Acid / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D002034:Bumetanide; D002712:Chlorides; D051860:Fragile X Messenger Ribonucleoprotein 1; D010121:Oxytocin; D014635:Valproic Acid; D005680:gamma-Aminobutyric Acid