Neutrophil Extracellular Traps In Psychiatric Disorders

Neutrophils are the largest group of innate immune cells in the mammalian immune system.They have a wide range of potent antimicrobial substances that are stored in particles.The functions of neutrophils include: phagocytosis,degranulation and release of neutrophil extracellular traps(NETs).Although its role in activating the immune system has been well established,its functions in neuro-immune interactions remain elusive until in recent years.In addition,its role in neurodegenerative diseases has been reported,but the specific mechanisms of neutrophils in psychiatric disorders remain unclear.In this research,we explored the biological mechanisms underlying the effects of neutrophil-associated inflammation on psychiatric disorders from two perspectives.Firstly,we used a mouse model of depression by intraperitoneal injection of lipopolysaccharide(LPS).It was found that the levels of inflammatory factors in the peripheral and brain of the mouse were increased with a large number of NETs produced.Peptide acyl arginine deiminase(PAD4)is an essential protein for citrullinated histone 3 release during the production of extracellular traps in neutrophil.Knockout(KO)of the gene encoding PAD4 completely block the production of NETs.When PAD4 KO mice were used to establish a depression model,it was found that the peripheral and neuroinflammatory levels and depression-like behaviors of the mice were significantly lower than those of the control group.On the other hand,some patients with schizophrenia experience metabolic side effects such as diabetes symptoms and weight gain after taking the antipsychotic olanzapine.We found that the neutrophils in peripheral blood can produce NETs and induce inflammation in patients taking the drug,which may be associated with these side effects.It has also been confirmed in the animal model that olanzapine can induce NETs and cause metabolism-related side effects.PAD4 KO mice did not exhibit the metabolic abnormalities associated with olanzapine administration by blocking NETs production.In summary,neutrophil extracellular traps may play an important role in the pathogenesis of psychiatric disorders.This study provides new insights into the mechanisms-underlying psychiatric disorders.