Chenhui Ji: Center for Translational Neurodegeneration and Regenerative Therapy, Tongji Hospital Affiliated to Tongji University School of Medicine, Shanghai 200065, China.
Yalin Tang: Center for Translational Neurodegeneration and Regenerative Therapy, Tongji Hospital Affiliated to Tongji University School of Medicine, Shanghai 200065, China.
Yanyan Zhang: Center for Translational Neurodegeneration and Regenerative Therapy, Tongji Hospital Affiliated to Tongji University School of Medicine, Shanghai 200065, China.
Xiaoyan Huang: Center for Translational Neurodegeneration and Regenerative Therapy, Tongji Hospital Affiliated to Tongji University School of Medicine, Shanghai 200065, China.
Congcong Li: Center for Translational Neurodegeneration and Regenerative Therapy, Tongji Hospital Affiliated to Tongji University School of Medicine, Shanghai 200065, China.
Yuhong Yang: Center for Translational Neurodegeneration and Regenerative Therapy, Tongji Hospital Affiliated to Tongji University School of Medicine, Shanghai 200065, China.
Qihui Wu: Translational Research Institute of Brain and Brain-Like Intelligence, Shanghai Fourth People's Hospital Affiliated to Tongji University School of Medicine, Shanghai 200081, China.
Xiaohuan Xia: Center for Translational Neurodegeneration and Regenerative Therapy, Tongji Hospital Affiliated to Tongji University School of Medicine, Shanghai 200065, China; Translational Research Institute of Brain and Brain-Like Intelligence, Shanghai Fourth People's Hospital Affiliated to Tongji University School of Medicine, Shanghai 200081, China; Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Clinical Research Center for Anesthesiology and Perioperative Medicine, Translational Research Institute of Brain and Brain-Like Intelligence, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai 200434, China; Shanghai Frontiers Science Center of Nanocatalytic Medicine, Tongji University, Shanghai 200331, China.
Qingyuan Cai: Franklin and Marshall College, 415 Harrisburg Avenue, Lancaster, PA 17603, USA.
Xin-Rui Qi: Center for Translational Neurodegeneration and Regenerative Therapy, Tongji Hospital Affiliated to Tongji University School of Medicine, Shanghai 200065, China. Electronic address: xinruiqi@tongji.edu.cn.
Jialin C Zheng: Center for Translational Neurodegeneration and Regenerative Therapy, Tongji Hospital Affiliated to Tongji University School of Medicine, Shanghai 200065, China; Translational Research Institute of Brain and Brain-Like Intelligence, Shanghai Fourth People's Hospital Affiliated to Tongji University School of Medicine, Shanghai 200081, China; Collaborative Innovation Center for Brain Science, Tongji University, Shanghai 200092, China; Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Clinical Research Center for Anesthesiology and Perioperative Medicine, Translational Research Institute of Brain and Brain-Like Intelligence, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai 200434, China; Shanghai Frontiers Science Center of Nanocatalytic Medicine, Tongji University, Shanghai 200331, China. Electronic address: jialinzheng@tongji.edu.cn.
An abnormal glutamate signaling pathway has been proposed in the mechanisms of autism spectrum disorder (ASD). However, less is known about the involvement of alterations of glutaminase 1 (GLS1) in the pathophysiology of ASD. We show that the transcript level of GLS1 is significantly decreased in the postmortem frontal cortex and peripheral blood of ASD subjects. Mice lacking Gls1 in CamKIIα-positive neurons display a series of ASD-like behaviors, synaptic excitatory and inhibitory (E/I) imbalance, higher spine density, and glutamate receptor expression in the prefrontal cortex, as well as a compromised expression pattern of genes involved in synapse pruning and less engulfed synaptic puncta in microglia. A low dose of lipopolysaccharide treatment restores microglial synapse pruning, corrects synaptic neurotransmission, and rescues behavioral deficits in these mice. In summary, these findings provide mechanistic insights into Gls1 loss in ASD symptoms and identify Gls1 as a target for the treatment of ASD.
