Researchers at UC Davis have published a study that illustrates how maternal immune activation could affect neurodevelopment in offspring.
Common characteristics that underlie many neuropsychiatric disorders such as autism spectrum disorder, schizophrenia, attention-deficit/hyperactivity disorder (ADHD) and bipolar disorder suggest they may share common causes. Epidemiological and clinical studies have identified links between these disorders and a family history of immune conditions. Most notably, mothers who have experienced increased immune activity during pregnancy are more likely to have a child with one of these neuropsychiatric disorders.
Led by Paul Ashwood, professor in the UC Davis Department of Medical Microbiology and Immunology, the study demonstrated that young mice showed increased hyperactivity and repetitive behaviors when mothers were exposed to allergens. The study findings were published in a paper entitled “Behavioral impact of maternal allergic-asthma in two genetically distinct mouse strains” in the journal Brain, Behavior, and Immunity.
In the study, researchers exposed two different strains of mice to ovalbumin (an allergen in egg whites) to induce asthma/allergy. The team found that the allergic reaction increased inflammatory cytokines in the mothers and induced ADHD and autism-like behaviors in their progeny.
Offspring of both mouse strains exhibited hyperactive and repetitive behaviors. However, one strain showed more impaired social interactions (such as going nose-to-nose and sniffing each other) compared to the other, hinting that genetic differences may play a key role. The mothers’ immune profiles also varied by strain and may relate to the differences in behavioral outcomes.
“By inducing allergies/asthma during gestation, we observed significant changes in juvenile social behaviors,” said Ashwood, a researcher with the UC Davis MIND Institute. “They were less social and had higher rates of repetitive behaviors. This may suggest that the unique cascade of inflammatory responses produced during allergies/asthma in the mothers led to the behavioral changes.”
These findings illuminate a potential pathway by which maternal inflammation may set the stage for a variety of neurodevelopmental issues. Though the studies did not investigate them, these immune/developmental issues could potentially generate neurodegenerative conditions associated with aging, such as Parkinson’s and Alzheimer’s.
“When we’re thinking about the immune response, certain inflammatory triggers such as asthma, allergies, infections or autoimmunity might have downstream effects on the behavior of the offspring,” Ashwood said. “This study is an early step toward understanding how inflammation affects neurodevelopment. Future investigations will tease out how these mechanisms affect synaptic pathways, brain growth, neuron proliferation and other aspects of neurodevelopment.”
The mouse model demonstrating the link between immune responses and neurodevelopmental disorders may reveal targets for therapy and prevention, Ashwood added, as well as novel interactions between immune signaling and neurological development for future research.
Other authors were: Jared J. Schwartzer and Morgan A. Coburn at Mount Holyoke College, and Milo Careaga, Destanie R. Rose and Heather K. Hughes at UC Davis.
This study was supported by the National Institutes of Health (R15HD082638 andU54HD079125), NARSAD Foundation, Jane Botsford Johnson Foundation, Peter Emch Foundation and Autism Speaks Foundation.