Summary: Previous research has shown that infections during pregnancy can increase the risk of autism spectrum disorder (ASD) and other psychiatric conditions in offspring. A new study from the University of Copenhagen explains how maternal infection disrupts neural development in the fetal brain and demonstrates that the timing of maternal inflammation critically influences the degree and type of risk for later mental health problems.
Source: University of Copenhagen
The mother’s health strongly influences fetal brain development. Nutrition, stress, hormones and immune activity in the mother all play essential roles in healthy neural development. Severe maternal infections have long been associated with elevated risk for psychiatric disorders such as schizophrenia and autism in exposed children, based on human epidemiology and animal studies.
Researchers at the Biotech Research and Innovation Centre (BRIC), University of Copenhagen, have now traced how maternal inflammation alters neuronal development in mice. Their findings, published in Molecular Psychiatry, reveal specific disruptions to the development of cortical GABAergic interneurons—cells that provide inhibitory control across cortical circuits. These disruptions begin in precursor cell populations and persist through neuronal maturation, producing lasting alterations in brain circuitry.
“Prior studies and clinical observations have linked maternal infection to increased risk of psychiatric disorders in offspring, but the precise developmental steps affected were unclear,” says Konstantin Khodosevich, Associate Professor at BRIC. “This study maps the affected stages of interneuron development and shows how maternal inflammation can lead to cognitive and behavioral deficits.”
Immediate and long-lasting effects on interneuron development
The Copenhagen team examined multiple stages of interneuron development in mice exposed to maternal inflammation. They found that the maternal immune response altered the proliferation of precursor cells, disrupted migration and positioning of neuroblasts, and impaired neuronal maturation. These effects were particularly pronounced for cortical GABAergic interneurons, which play a central role in balancing excitation and inhibition in the cortex.
Because these disruptions appear at several distinct developmental steps, they create a cascade of deficits—from the time interneurons are born until they reach maturity. The cumulative impact produces multiple “hits” to the developing inhibitory system, with structural and functional consequences that persist into postnatal life.
Behaviorally, offspring of inflamed mothers displayed deficits that mirror aspects of human psychiatric conditions. Newborn mice showed reduced prepulse inhibition (a measure of sensorimotor gating), altered social behaviors, and cognitive impairments—outcomes consistent with disruption of inhibitory circuits during development.
“Studying these processes in humans presents major ethical and technical challenges, which is why animal models are essential,” explains Khodosevich. “Psychiatric disorders are complex and multifactorial; mapping the developmental mechanisms affected by maternal inflammation helps us understand potential origins of cognitive and behavioral deficits.”
Timing matters: stage- and subtype-specific vulnerability
A key discovery is that the timing of maternal infection determines which precursor cell populations and interneuron subtypes are affected. Inflammation at different gestational stages selectively disrupted distinct interneuron subtypes, producing varied patterns of reduced cell numbers, altered cortical distribution, and changes in morphology and cellular properties. This stage-dependent vulnerability offers a plausible mechanism for why maternal insults can lead to diverse psychiatric outcomes depending on when during pregnancy they occur.
The research team is now pursuing deeper analysis of the molecular signaling pathways that mediate these effects. Identifying the specific inflammatory signals and downstream mechanisms that impair interneuron development will be crucial for understanding how maternal health influences neurodevelopmental risk.
Source:
University of Copenhagen
Media Contacts:
Konstantin Khodosevich – University of Copenhagen
Image Source:
The image is in the public domain.
Original Research: Closed access
“Maternal inflammation has a profound effect on cortical interneuron development in a stage and subtype-specific manner.” Navneet A. Vasistha et al., Molecular Psychiatry. DOI: 10.1038/s41380-019-0539-5.
Abstract (summary)
Severe infections during pregnancy are a significant risk factor for cognitive impairment in offspring. Evidence suggests maternal inflammation disrupts cortical GABAergic interneuron development, contributing to later cognitive deficits. This study shows maternal inflammation affects multiple developmental steps—precursor proliferation, migration and positioning of neuroblasts, and neuronal maturation—and that distinct interneuron subtypes are differentially vulnerable depending on developmental timing. The findings indicate that maternally derived insults produce stage-dependent effects on interneuron populations, offering insight into the complex origins of cognitive and behavioral disorders linked to prenatal inflammation.