Glutaminase 1 deficiency confined in forebrain neurons causes autism spectrum disorder-like behaviors

• DOI: 10.1016/j.celrep.2023.112712
• Publication Date: 2023-06-28T18:51:24Z
• Authors: Chenhui Ji; Yalin Tang; Yanyan Zhang; Xiaoyan Huang; Congcong Li; Yuhong Yang; Qihui Wu; Xiaohuan Xia; Qingyuan Cai; Xin-Rui Qi; Jialin C. Zheng
• Keywords: Forebrain; Glutaminase

An abnormal glutamate signaling pathway has been proposed in the mechanisms of autism spectrum disorder (ASD). However, less is known about involvement alterations glutaminase 1 (GLS1) pathophysiology ASD. We show that transcript level GLS1 significantly decreased postmortem frontal cortex and peripheral blood ASD subjects. Mice lacking Gls1 CamKIIα-positive neurons display a series ASD-like behaviors, synaptic excitatory inhibitory (E/I) imbalance, higher spine density, receptor expression prefrontal cortex, as well compromised pattern genes involved synapse pruning engulfed puncta microglia. A low dose lipopolysaccharide treatment restores microglial pruning, corrects neurotransmission, rescues behavioral deficits these mice. In summary, findings provide mechanistic insights into loss symptoms identify target for