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Principal Investigator: Jared Schwartzer
Organization: MOUNT HOLYOKE COLLEGE
Fiscal Year: 2024
Award: $443,738
Funding agency: National Institute of Mental Health
PROJECT SUMMARY/ABSTRACT
The state of the mother's immune system during pregnancy plays an important role in fetal
development, and disruptions in this immune balance are associated with a range of neuropsychiatric
and neurodevelopmental disorders. Epidemiological and clinical studies have revealed associations
between neurodevelopmental disorders including Autism Spectrum Disorder (ASD) and Attention Deficit
Hyperactivity Disorder (ADHD) and family history of immune system dysfunction, most notably allergies
and asthma. Over the past three decades, analogous increases have been reported in both the
incidence of ASD, ADHD, and immune-related disorders, particularly immune hypersensitivities that
include allergies and asthma. Several case-control reports have noted that mothers with elevated
allergic-associated cytokines during pregnancy are at greater risk of having a child who was later
diagnosed with ASD or ADHD. These data raise the hypothesis that maternal allergic asthma (MAA)
produces neurobehavioral deficits in offspring and highlight a yet undetermined link between the
maternal immune system and risk of neurodevelopmental disorders. Using a validated mouse model of
allergic asthma, we have demonstrated that offspring of MAA dams exhibit behavioral deficits
characterized by decreased social interactions and increased repetitive behaviors. This proposal will
extend these findings by exploring the mechanistic contribution of the allergic asthma-associated
cytokine interleukin-4 (IL-4) in driving the link between MAA on offspring brain and behavior
development. Specifically we will [1] determine the contribution of maternal IL-4 signaling in
precipitating neurodevelomental deficits, [2] characterize the safety and efficacy of the allergic asthma
medication dupilumab, an IL-4 receptor antagonist, in preventing the effects of MAA on offspring
behavior, [3] examine the neuroimmunological consequences of MAA on offspring brain development,
and [4] associate changes in neuroimmune signaling with behavioral outcomes. The results of these
experiments will determine the extent to which maternal IL-4 signaling in allergic asthma contributes to
offspring neurodevelopmental deficits and inform future therapeutic interventions for mitigating the
effects of maternal asthma in at-risk populations.
Terms: <0-11 years old><21+ years old><AD/HD><ADHD><ASD><Adult><Adult Children><Adult Daughters><Adult Human><Adult Offspring><Adult Sons><Allergic><Allergic asthma><Allergy><Asthma><Attention deficit hyperactivity disorder><Autism><Autistic Disorder><Autoimmune Diseases><Automobile Driving><B Cell-Activating Factor Receptor><B cell growth factor><B-Cell Differentiation Factor-1><B-Cell Growth Factor-1><B-Cell Growth Factor-I><B-Cell Proliferating Factor><B-Cell Stimulating Factor><B-Cell Stimulating Factor-1><B-Cell Stimulation Factor-1><B-Cell Stimulatory Factor-1><BCDF-1><BCGF><BCGF-1><BCSF 1><BSF-1><BSF1><Behavior><Behavior assessment><Behavioral><Binetrakin><Biological><Biological Markers><Brain><Brain Inflammation><Brain Nervous System><Bronchial Asthma><CD124 Antigens><CDw124 Antigen><Cell Communication and Signaling><Cell Signaling><Characteristics><Child><Child Youth><Children (0-21)><Chronic Disease><Chronic Illness><Clinical Research><Clinical Study><Data><Developing fetus><Development><Diagnosis><Disease><Disorder><Dose><Drugs><Early Infantile Autism><Economically Deprived Population><Encephalitis><Encephalon><Environment><Environmental Factor><Environmental Risk Factor><Epidemiologic Research><Epidemiologic Studies><Epidemiological Studies><Epidemiology Research><Equilibrium><Ethnic Origin><Ethnicity><Exhibits><Extrinsic asthma><Family Medical History><Family Medical History Epidemiology><Family history of><Fetal Development><Future><Gestation><Groups at risk><High Prevalence><Human><Hypersensitivity><IL-4><IL-4 Receptors><IL4 Protein><IL4 Receptors><Immune><Immune Diseases><Immune Disorders><Immune Dysfunction><Immune System Diseases><Immune System Disorder><Immune System Dysfunction><Immune System and Related Disorders><Immune signaling><Immunes><Immunodeficiency and Immunosuppression Disorders><Immunologic Diseases><Immunological Diseases><Immunological Dysfunction><Immunological System Dysfunction><Incidence><Infantile Autism><Institution><Interleukin 4 Receptor><Interleukin-4><Interleukin-4 Precursor><Interleukin-4 Receptor Alpha><Interleukins><Intracellular Communication and Signaling><Kanner's Syndrome><Link><Lymphocyte Stimulatory Factor 1><MCGF-2><Mast Cell Growth Factor-2><Measures><Medication><Mice><Mice Mammals><Modern Man><Mothers><Murine><Mus><NIMH><National Institute of Mental Health><Neurodevelopmental Deficit><Neurodevelopmental Disorder><Neuroimmune><Neurological Development Disorder><People at risk><Peripheral><Persons at risk><Pharmaceutical Preparations><Play><Populations at Risk><Predominantly Hyperactive-Impulsive Type Attention-Deficit Disorder><Predominantly Hyperactive-Impulsive Type Hyperactivity Disorder><Pregnancy><Probabilistic Models><Probability Models><Public Health><RDoC><Reporting><Research><Research Domain Criteria><Risk><Role><Safety><Sampling><Science><Severities><Signal Transduction><Signal Transduction Systems><Signaling><Social Behavior><Social Interaction><Socioeconomically disadvantaged><Statistical Models><Students><T-Cell Growth Factor 2><Testing><Therapeutic Intervention><Underrepresented Groups><Underrepresented Populations><United States><Variant><Variation><adulthood><after pregnancy><allergen response><allergic response><allergy response><antagonism><antagonist><atopic asthma><autism spectral disorder><autism spectrum disorder><autistic children><autistic spectrum disorder><autoimmune condition><autoimmune disorder><autoimmunity disease><balance><balance function><behavior measurement><behavior outcome><behavior phenotype><behavior prediction><behavioral assessment><behavioral impairment><behavioral measure><behavioral measurement><behavioral outcome><behavioral phenotyping><behavioral prediction><bio-markers><biologic><biologic marker><biological signal transduction><biomarker><career><case control><case-controlled><children on the autism spectrum><children with ASD><children with autism><children with autism spectrum disorder><chronic disorder><cytokine><determine efficacy><developmental><driving><drug/agent><economically deprived group><economically deprived people><economically disadvantaged group><economically disadvantaged individual><economically disadvantaged people><economically disadvantaged population><efficacy analysis><efficacy assessment><efficacy determination><efficacy evaluation><efficacy examination><environmental risk><epidemiologic investigation><epidemiology study><evaluate efficacy><examine efficacy><experience><experiment><experimental research><experimental study><experiments><extrinsic allergic asthma><fetal><gender diverse><impaired behavior><improved><innovate><innovation><innovative><intervention therapy><kids><late life><maternal immune system><mother immune system><mouse model><murine model><neurobehavioral><neurodevelopment effect><neurodevelopmental disease><neurodevelopmental effect><neuropsychiatric disease><neuropsychiatric disorder><offspring><pharmacologic><post pregnancy><prevent><preventing><racial minority><repetitive behavior><social role><socio-economic disadvantage><socio-economically disadvantaged><socio-economically underprivileged><sociobehavior><sociobehavioral><socioeconomic disadvantage><socioeconomically underprivileged><statistical linear mixed models><statistical linear models><tool><under representation of groups><under represented groups><under represented people><under represented populations><underclass><undergraduate research><underrepresentation of groups><underrepresented people><urban environment><urban setting><youngster>