Neuronal Nitric Oxide Synthase Knockdown Within Basolateral Amygdala Induces Autistic-Related Phenotypes and Decreases Excitatory Synaptic Transmission in Mice

Frontiers in Neuroscience

Lingshan Gou¹  Leiming Liu²  Daoqi Mei³  Zhigang Yang³  Huichun Zhang⁴  Chao Gao⁴  Quanfeng Fang⁵  Linfei Li⁶  Yaodong Zhang⁶  Jing Liu⁶  Xiaona Wang⁶  Yinsen Song⁷  Jinxiu Xu⁸ 

[1] Center for Genetic Medicine, Xuzhou Maternity and Child Health Care Hospital, Xuzhou, China;Department of Medical Assistance, Children’s Hospital Affiliated to Zhengzhou University, Zhengzhou, China;Department of Neurology, Children’s Hospital Affiliated to Zhengzhou University, Zhengzhou, China;Department of Rehabilitation, Children’s Hospital Affiliated to Zhengzhou University, Zhengzhou, China;Healthcare Department, Children’s Hospital Affiliated to Zhengzhou University, Zhengzhou, China;Henan Key Laboratory of Children’s Genetics and Metabolic Diseases, Henan Neurodevelopment Engineering Research Center for Children, Children’s Hospital Affiliated to Zhengzhou University, Zhengzhou, China;People’s Hospital Affiliated to Henan University of Chinese Medicine, Zhengzhou, China;School of Basic Medicine, Sanquan Medical College, Xinxiang, China;

关键词: neuronal nitric oxide synthase;    autism spectrum disorder;    interneuron;    synaptic transmission;    basolateral amygdala;   

DOI  :  10.3389/fnins.2020.00886

来源: DOAJ

【 摘 要 】

Autism spectrum disorder (ASD) is a heterogeneous group of neurodevelopmental disorders characterized by deficits in communication, impaired social interaction, and repetitive or restricted interests and behaviors. We have recently shown that neuronal nitric oxide synthase (nNOS) expression was reduced in the basolateral amygdala of mice after postnatal valproic acid exposure. However, the specific role of nNOS downregulation in mice remains to be elucidated. Herein, we investigated the behavioral alternations of naive mice with a recombinant adeno-associated virus (rAAV)-mediated knockdown of nNOS in a comprehensive test battery, including the social interaction, marble burying, self-grooming, and open field tests. Further, the electrophysiological and surface expression changes induced by nNOS deficiency of the basolateral amygdala in these animals were examined. Our results show that nNOS knockdown displayed typical symptoms of ASD-like behaviors, such as reduced social interaction and communication, elevated stereotypes, and anxiety in mice. Surprisingly, we found that nNOS knockdown exhibited greatly reduced excitatory synaptic transmission concomitant with the lower surface expression of GluN2B-containing N-methyl-D-aspartate receptors and postsynaptic density protein 95 in mice. These findings support a notion that dysregulation of nNOS might contribute to ASD-associated phenotypes, with disease pathogenesis most likely resulting from deficits in excitatory synaptic transmission.

【 授权许可】

Unknown