PLoS Biology: over activation of the immune system leading to schizophrenia

January 17, 2020 / BIOON / -- on January 14, Ashley comer and Alberto Cruz mart í n of Boston University published a new study in the open access journal PLoS Biology, which showed that the over activation of previously schizophrenia related immune system genes can affect nerves and behaviors in mice This discovery provides mechanical support for the importance of the gene in the development of schizophrenia, and may provide a new way for the development of treatment Previously, in large-scale genome-wide association studies, it has been proved that genetic variants that enhance C4 gene activity, which encode part of the so-called "complement" cascade response of the immune system, will increase the risk of schizophrenia However, it is not clear how this variant may contribute to the development of schizophrenia (image source: www Pixabay Com) it is well known that during normal brain development, complement adheres to the synapses of neurons and attracts microglia (immune cells in the brain), thus phagocytizing synaptic substances in a process called "synaptic pruning" If not, this process can lead to abnormal connections in the brain The loss of synapses in prefrontal cortex of frontal lobe is a sign of schizophrenia, which makes the author question whether C4 gene hyperactivity may promote the development of schizophrenia through the wrong regulation of microglia on complement mediated synaptic pruning When they overexpressed complement C4 in the prefrontal cortex of mice, they found that the phagocytosis level of microglia in synapses increased, the functional connectivity between neurons decreased, and the nature of neuron membrane changed Schizophrenia is characterized by inadequate social cognition and interaction, which usually precedes the development of psychosis The authors found that young mice with excess complement C4 levels spent less time searching for mothers than the control mice, while adult mice spent less time interacting with their new cage mates In conclusion, these results suggest that the genetic association between increased C4 gene activity and schizophrenia may be at least partly due to an inappropriate increase in synaptic pruning during brain development "This critical developmental window may provide an opportunity for intervention to change the trajectory of schizophrenia," said senior researcher Cruz Martin Although there are few approved drugs that can block the complement system, this is a hot topic in drug research, and these findings may stimulate further interest in this method Information sources: hyperactive immune system gene causes schizophrenia like changes in mice original sources: Ashley L comer, tushare jinadasa, Balaji sriram, rhushikesh a Phadke, Lisa n kretsge, Thanh P h Nguyen, Giovanna antognetti, James P Gilbert, jungjoon Lee, Elena R Newmark, Frances S Hausmann, saraann Rosenthal, Kevin Liu Kot, Yenyu Liu, William W Yen, Borislav Dejanovic, Alberto Cruz-Martín Increased expression of schizophrenia-associated gene C4 leads to hypoconnectivity of prefrontal cortex and reduced social interaction PLOS Biology, 2020; 18 (1): e3000604 DOI: 10.1371/journal.pbio.3000604