JAN 19, 2020 5:20 PM PST

Overactive Immune Gene May Cause Schizophrenia

WRITTEN BY: Kara Marker

A windy road links excessive activity of the “C4” gene to the development of schizophrenia. Researchers began to study C4 activity as part of new, preliminary research to both further understand how this condition develops and potentially develop new therapeutic targets.

C4 is part of the immune system’s “complement cascade,” a system of proteins that work together to initiate inflammatory responses triggered by infection. Proteins expressed by the C4 gene “stick” to neuronal synapses and recruit microglia to the scene. Microglia are the resident immune cells in the brain, and during healthy brain function, they clean up synaptic debris through a process called “synaptic pruning.”

Microglial dysfunction, however, can lead to disconnectivity in the brain. And disconnectivity stemming from loss of synapses is a “hallmark” of schizophrenia, which leads scientists to ask a series of questions. Is C4 overactivity leading to excessive microglial synaptic pruning as directed by the complement cascade? Is this excessive synaptic pruning leading to the development of schizophrenia?

In the past, C4 genetic variants increasing the gene’s activity have been associated in genome-wide association studies (GWAS) with increased risk of schizophrenia. In the present study, researchers conduct a novel test of what happens when the C4 gene is directly overexpressed.

Specifically, the study initiated C4 overexpression in the prefrontal cortex of mice, which led to increases in microglial synaptic pruning activity. This in turn resulted in “reduced functional connectivity between neurons” and ultimately led to fundamental changes in the status of neuronal membranes.

As a result of this chain reaction, researchers observed behavioral signs of schizophrenia in mice. Essentially, mice with overactive C4 - juvenile and adult - spent less time socializing than control mice.

"This critical developmental window may provide an opportunity to intervene to alter the developmental trajectory of schizophrenia," explained senior investigator Alberto Cruz-Martín.

Sources: PLoS Biology, “Immunobiology: The Immune System in Health and Disease

About the Author
Master's (MA/MS/Other)
I am a scientific journalist and enthusiast, especially in the realm of biomedicine. I am passionate about conveying the truth in scientific phenomena and subsequently improving health and public awareness. Sometimes scientific research needs a translator to effectively communicate the scientific jargon present in significant findings. I plan to be that translating communicator, and I hope to decrease the spread of misrepresented scientific phenomena! Check out my science blog: ScienceKara.com.
You May Also Like
NOV 17, 2022
Cancer
Anti-Aging Supplement Linked to Aggressive Breast Cancer
Anti-Aging Supplement Linked to Aggressive Breast Cancer
Vitamin B3, also known as niacin, is a generic name for a group of biochemical compounds, including nicotinamide ribosid ...
DEC 05, 2022
Drug Discovery & Development
Characterization and Manufacturing of AAVs for Gene Therapy
Characterization and Manufacturing of AAVs for Gene Therapy
The backdrop upon which every successful gene therapy is developed is the ability to safely and specifically target cell ...
JAN 04, 2023
Health & Medicine
Jack-of-All-Trades Psychiatric Treatment Had Unknown Anti-Inflammatory Actions
Jack-of-All-Trades Psychiatric Treatment Had Unknown Anti-Inflammatory Actions
The new anti-psychotic lumateperone was developed to treat schizophrenia and bipolar I and II disorder in adults. But wh ...
JAN 13, 2023
Immunology
B Cell Surface Features Revealed by Advanced Microscopy
B Cell Surface Features Revealed by Advanced Microscopy
With an advanced technique called lattice light sheet microscopy, scientists have revealed structures on the surface of ...
JAN 16, 2023
Immunology
How the Immune System Tolerates Gut Bacteria
How the Immune System Tolerates Gut Bacteria
Our immune system is built to detect foreign invaders, pathogens, and debris, and eliminate them. So how dies it deal wi ...
JAN 26, 2023
Immunology
An Improved Understanding of 'Original Antigenic Sin'
An Improved Understanding of 'Original Antigenic Sin'
"Original antigenic sin" is a phenomenon that was identified in 1960; it refers to s situation in which the im ...
Loading Comments...