Oxytocin-Mediated GABA Inhibition During Delivery Attenuates Autism Pathogenesis in Rodent Offspring

被引：431
作者：
Tyzio, Roman [1 ,2 ]
Nardou, Romain [3 ]
Ferrari, Diana C. [3 ]
Tsintsadze, Timur [1 ,2 ,3 ]
Shahrokhi, Amene [3 ]
Eftekhari, Sanaz [3 ]
Khalilov, Ilgam [1 ,2 ]
Tsintsadze, Vera [1 ,2 ]
Brouchoud, Corinne [1 ,2 ]
Chazal, Genevieve [1 ,2 ]
Lemonnier, Eric [4 ]
Lozovaya, Natalia [1 ,2 ]
Burnashev, Nail [1 ,2 ]
Ben-Ari, Yehezkel [1 ,2 ,3 ]
机构：
[1] INSERM, Mediterranean Inst Neurobiol INMED, U901, F-13258 Marseille, France
[2] Aix Marseille Univ, UMR 901, Marseille, France
[3] Neurochlore, F-13273 Marseille 09, France
[4] Lab Neurosci Brest EA4685, Brest, France
来源：
SCIENCE | 2014年 / 343卷 / 6171期
关键词：
RANDOMIZED CONTROLLED-TRIAL; SPECTRUM DISORDERS; VASOPRESSIN; CHILDREN; NEURONS; BRAIN;
D O I：
10.1126/science.1247190
中图分类号：
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号：
07 ; 0710 ; 09 ;
摘要：
We report that the oxytocin-mediated neuroprotective g-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 naive 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.
引用
收藏
页码：675 / 679
页数：5
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