Study Suggests Exposure to Increased Maternal Immune Response Could Elevate Prenatal Risk for Schizophrenia
Study links disruption of embryo's development of cortical interneurons with later development of neuropsychiatric disorders.
Epidemiological studies have frequently associated increased immune responses in pregnant women brought on by such factors as maternal infection, autoimmune disorders and asthma with later development of neuropsychiatric disorders, including schizophrenia and autism spectrum disorders, in their children.
A team of researchers at New York Medical College (NYMC), led by Sangmi Chung, Ph.D., associate professor of cell biology and anatomy, neurology and of psychiatry and behavioral sciences, recently conducted a study investigating the impact that the activation of microglia (a type of neuronal support cell that functions primarily as an immune cell) can have on an embryo's development of cortical interneurons, a specific class of neurons that regulates information processing. Their findings, published in Nature Neuroscience, suggest that activated microglia can cause metabolic disruptions that adversely impact the prenatal development of cortical interneurons and increases an individual’s risk for developing schizophrenia later in life.
Coauthors on the study included Weihua Huang, Ph.D., associate professor of pathology, Hae-Young Kim, M.S., Dr.P.H., associate professor of public health, Chiderah Abani, GSBMS student, Cameron Beaudreault, GSBMS Class of 2020, SOM Class of 2024, Sasha Gonzalez, GSBMS student, Youxin Guan, SOM Class of 2021 and Derek Le, GSBMS student.
Because past research has found that individuals with schizophrenia present abnormal patterns in the functioning of cortical interneurons, the NYMC researchers generated cortical interneurons using induced pluripotent stem cells (iPSCs), a technological tool that allows neuroscientists to reprogram cells that are extracted from human tissue samples.
"While we now known that cortical interneurons are affected by maternal immune activation, the mechanism through which they are affected is still poorly understood," said Dr. Chung. "Since the human embryo is not accessible for mechanistic studies, we used induced pluripotent stem cells (iPSC)-derived human cortical interneurons to investigate how inflammation during development affects this vulnerable population of neurons."
After creating the cells, the research team co-cultured them either with or without activated microglial cells and observed the effects that these two procedures had on cortical interneurons generated from the tissue of those with no neuropsychiatric disorders and on those derived from that of patients with schizophrenia.
"We found that the metabolism of cortical interneurons is compromised under inflammatory condition during development, which showed prolonged impact in cortical interneurons derived from schizophrenia iPSCs but not healthy control iPSCs," said Dr. Chung. "Our findings highlight the existence of interactions between schizophrenia genetic backgrounds and environmental risk factors."
Most notably, the findings from the study suggest that the activation of microglia can cause metabolic disruptions in developmental cortical interneurons. Additionally, in the cortical interneurons generated from the tissue of individuals with no neuropsychiatric disorders, the metabolic deficits were not present after the activated microglia were removed, while they persisted in patients affected by schizophrenia.
“We now plan to pursue further studies investigating the detailed mechanisms and pathways that are affected by inflammatory environments surrounding cortical interneurons," said Dr. Chung.
Portions of this article were excerpted from an article in Medical Express.