Abstract
The state of the mother's immune system during pregnancy has an important role in fetal development and disruptions in the balance of this system are associated with a range of neurologic, neuropsychiatric and neurodevelopmental disorders. Epidemiological and clinical reports reveal various clues that suggest a possible association between developmental neuropsychiatric disorders and family history of immune system dysfunction. Over the past three decades, analogous increases have been reported in both the incidence of neurodevelopmental disorders and immune-related disorders, particularly allergy and asthma, raising the question of whether allergic asthma and characteristics of various neurodevelopmental disorders share common causal links. We used a mouse model of maternal allergic asthma to test this novel hypothesis that early fetal priming with an allergenic exposure during gestation produces behavioral deficits in offspring. Mothers were primed with an exposure to ovalbumin (OVA) before pregnancy, then exposed to either aerosolized OVA or vehicle during gestation. Both male and female mice born to mothers exposed to aerosolized OVA during gestation exhibited altered developmental trajectories in weight and length, decreased sociability and increased marble-burying behavior. Moreover, offspring of OVA-exposed mothers were observed to have increased serotonin transporter protein levels in the cortex. These data demonstrate that behavioral and neurobiological effects can be elicited following early fetal priming with maternal allergic asthma and provide support that maternal allergic asthma may, in some cases, be a contributing factor to neurodevelopmental disorders.
Highlights
Developmental neuropsychiatric disorders are heterogeneous in their presentation and often share common behavioral characteristics across diagnoses
Social behavior deficits, including difficulties relating to others, impaired mood regulation and cognitive impairments are apparent in autism spectrum disorders (ASD), schizophrenia, attention deficit/hyperactivity disorder (ADHD) and bipolar disorder
Maternal allergy/asthma and offspring development JJ Schwartzer et al behavioral characteristics present across neurodevelopmental disorders including altered social behavior,[20,21] motor activity,[22] anxiety[23] and learning and memory impairments.[22,23]. These findings demonstrate a link between maternal immune activation and neurodevelopmental deficits, the translational validity of pathogen-induced fetal priming is limited as rates of pathogen infection in developed countries have markedly declined over the past century.[24]
Summary
Developmental neuropsychiatric disorders are heterogeneous in their presentation and often share common behavioral characteristics across diagnoses. Social behavior deficits, including difficulties relating to others, impaired mood regulation and cognitive impairments are apparent in autism spectrum disorders (ASD), schizophrenia, attention deficit/hyperactivity disorder (ADHD) and bipolar disorder. These shared characteristics represent plausible endophenotypes that may result from a common etiological mechanism. Bipolar disorder and schizophrenia emerge later in life, these disorders along with other neurodevelopmental disorders, such as ASD and ADHD, are thought to have developmental origins early in the prenatal period.[1,2,3] genetic factors are likely contributors to these disorders, heritability estimates indicate strong environmental contributions.[4] Of particular interest is the link between fetal gestation and the activation of the maternal immune system during critical periods of development. Epidemiological reports suggest a strong association between periods of maternal immune activation and an increased risk of having a child with a neurodevelopmental disorder.[5,6,7] This association is concerning given the parallel increases reported in the incidence of immunerelated disorders, in particular asthma and allergies, over the past decade.[8,9,10,11]
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