title: Lithium ameliorates autistic-like behaviors induced by neonatal isolation in rats.
abstract: Neonatal isolation is a widely accepted model to study the long-term behavioral changes produced by the early life events. However, it remains unknown whether neonatal isolation can induce autistic-like behaviors, and if so, whether pharmacological treatment can overcome it. Here, we reported that newborn rats subjected to individual isolations from their mother and nest for 1 h per day from postnatal days 1-9 displayed apparent autistic-like symptoms including social deficits, excessive repetitive self-grooming behavior, and increased anxiety- and depressive-like behaviors tested in young adult (postnatal days 42-56) compared to normal reared controls. Furthermore, these behavioral changes were accompanied by impaired adult hippocampal neurogenesis and reduced the ratio of excitatory/inhibitory synaptic transmissions, as reflected by an increase in spontaneous inhibitory postsynaptic current (sIPSC) and normal spontaneous excitatory postsynaptic current (sEPSC) in the hippocampal CA1 pyramidal neuron. More importantly, chronic administration of lithium, a clinically used mood stabilizer, completely overcame neonatal isolation-induced autistic-like behaviors, and restored adult hippocampal neurogenesis as well as the balance between excitatory and inhibitory activities to physiological levels. These findings indicate that neonatal isolation may produce autistic-like behaviors, and lithium may be a potential therapeutic agent against autism spectrum disorders (ASD) during development.
authors.affiliation: Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University Chongqing, China ; Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, Children's Hospital of Chongqing Medical University Chongqing, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Wu
authors.affiliation: Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University Chongqing, China ; Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, Children's Hospital of Chongqing Medical University Chongqing, China.
authors.forename: Yanrui
authors.initials: Y
authors.lastname: Bai
authors.affiliation: Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University Chongqing, China ; Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, Children's Hospital of Chongqing Medical University Chongqing, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Tan
authors.affiliation: Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University Chongqing, China ; Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, Children's Hospital of Chongqing Medical University Chongqing, China.
authors.forename: Hongjie
authors.initials: H
authors.lastname: Li
authors.affiliation: Ministry of Education Key Laboratory of Developmental Genes and Human Disease, Institute of Life Sciences, Southeast University Nanjing, China.
authors.forename: Shuting
authors.initials: S
authors.lastname: Xia
authors.affiliation: Ministry of Education Key Laboratory of Developmental Genes and Human Disease, Institute of Life Sciences, Southeast University Nanjing, China.
authors.forename: Xinxia
authors.initials: X
authors.lastname: Chang
authors.affiliation: Ministry of Education Key Laboratory of Developmental Genes and Human Disease, Institute of Life Sciences, Southeast University Nanjing, China.
authors.forename: Zikai
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University Chongqing, China ; Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, Children's Hospital of Chongqing Medical University Chongqing, China.
authors.forename: Weihui
authors.initials: W
authors.lastname: Zhou
authors.affiliation: Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University Chongqing, China ; Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, Children's Hospital of Chongqing Medical University Chongqing, China.
authors.forename: Tingyu
authors.initials: T
authors.lastname: Li
authors.affiliation: Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University Chongqing, China ; Brain Research Centre, University of British Columbia Vancouver, BC, Canada.
authors.forename: Yu Tian
authors.initials: YT
authors.lastname: Wang
authors.affiliation: Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University Chongqing, China ; Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, Children's Hospital of Chongqing Medical University Chongqing, China.
authors.forename: Zhifang
authors.initials: Z
authors.lastname: Dong
keywords: autism spectrum disorder; neonatal isolation; neurogenesis; social deficit; spontaneous inhibitory postsynaptic current