Maternal Allergic Asthma & Offspring Behavior Development

Over the past three decades, we have seen parallel increases in the incidence of both allergic asthma and autism spectrum disorders (ASD), raising the question of whether these two conditions are associated. Population-based studies have revealed a link between allergy-associated immune activation during pregnancy and increased risk of having a child later diagnosed with a neurodevelopment disorder. However, these studies only show correlation, not causation.  With all of this in mind, our lab explores maternal allergic asthma (MAA) as a potentially under-examined environmental factor influencing brain and behavior development.

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In collaboration with Dr. Paul Ashwood of the Medical Microbiology and Immunology department at the MIND Institute of University California, Davis, our lab has developed a model to test the causal link between maternal allergic asthma and offspring brain and behavior development.

Using this model, we apply a range of behavioral tasks designed to measure discrete components of social behavior in order to define critical periods during gestation when maternal allergic asthma disrupts neurobehavioral processes.  We then evaluate the role that asthma-related cytokines play in disrupting offspring development.


Automated Encoding of Complex Social Interactions

Social behavior deficits are at the core of many neurodevelopmental disorders stemming from a number of neurological and behavioral processes. Like other cognitive processes, individuals vary in their social skills, including ability to relate to others, recognition of empathy, and motivation to navigate novel social environments. Common animal behavior tasks narrowly measure basic deficits in social approach behavior, but are lacking depth in understanding the specific neurobiological mechanisms contributing to these behavioral changes. Our lab is developing a battery of tasks specifically designed to identify which components of the social brain are perturbed following genetic and environmental insults. Using computer-assisted tracking software and employing state-of-the-art behavioral assessments, we are working to tease apart discrete neural processes contributing to rodent social behavior including the emergence of social-specific reward processes, experience-induced social cognition, and social skill development. 

Computer-Driven Social Dyad Tracking

Obtaining efficient, reliable data in certain promising rodent behavior tasks can be very challenging, given the potentially objective nature of scoring these tasks. Faced with the challenges of achieving high quality and replicable data for some of our most exciting behavioral tasks, our lab has begun developing a novel marking system that enables us to differentiate mice of all genotypes through automated social dyad tracking software. Markers are non-toxic, easily applied without the need for restraint, and are available in a variety of colors to identify up to four mice at a time. This identification system enables us to encode a range of complex social behaviors, from social sniffing and approaching, to following and avoidance, using high-throughput and unbiased detections.


Gene-Environment Interactions

The causes of neurodevelopmental disorders stems from a combination of genetic and environmental factors. In order to untangle the complex gene-environment interactions that lead to neurodevelopmental disorders, we apply existing and novel translational animal models across mice of several genetic strains to identify how unique genetic predisposition exacerbate environmental insults. We are particularly interested in the consequences of pro-inflammatory factors in mice with immune system sensitivity. Much of our work has focused on the BTBR mouse, a strain that shows reductions in social interaction and increased repetitive motor behaviors compared to many other mice strains.


BTBR mice show persistent immune system dysregulation that closely resembles immune system alterations reported in autism. We have identified that when pregnant BTBR mice are exposed to a viral infection their heightened inflammatory response leads to exaggerated behavioral deficits in offspring compared to other strains. Interestingly, these exaggerated gene-by-environment interactions are more apparent in male offspring, which parallels the higher gender prevalence seen across developmental disorders.  For example, male BTBR offspring born from mothers exposed to a viral mimic (known as polyI:C) during pregnancy spend excessive time in repetitive motor grooming patterns compared to other BTBR mice and mice of other strains (C57Bl/6J). 

Gene by environment interactions in mouse behavior

Members of the Schwartzer Lab are continuing to explore how genetic differences in the BTBR strain, along with genetic susceptibility in other strains, lead to greater sensitivity to developmental exposure to immune and other environmental insults.

Neuro-Immune Brain Development

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    The serotonin synapse and the serotonin transporter (SERT) protein. These proteins are found in greater numbers in the brains of mice exposed to elevated maternal cytokines during fetal development.

The serotonin synapse and the serotonin transporter (SERT) protein. These proteins are found in greater numbers in the brains of mice exposed to elevated maternal cytokines during fetal development.

The immune system plays a crucial and very active role in healthy brain development. Changes in immune system signaling, through cytokines and chemokines, can dramatically alter how neurons grow, mature, and connect to one another. A major research focus in the Schwartzer Lab is exploring the intimate relationship between immune activity and neurotransmitter development. Much of our work to date has focused on the maturation of the serotonin system because of its role in both immune and nervous system function. Serotonin plays a vital role in brain development and mental health as disruptions in serotonin signaling are linked to a range of developmental and neuropsychiatric disorders. Currently, research efforts are exploring how changes in signaling of an immune molecule known as Interleukin-4 leads to disruptions in serotonin synapse proteins. Our initial findings point to an increase in the expression of the serotonin transporter protein (SERT) in the brains of offspring who were exposed to higher levels of maternal cytokines, including Interleukin-4, during fetal development.