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Maternal Interleukin-4 and allergic asthma in mouse offspring behavioral deficits

Award Number: R15MH119500
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 02/01/2019
PERIOD OF PERFORMANCE END DATE: 02/19/2027

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Maternal Interleukin-4 and allergic asthma in mouse offspring behavioral deficits - 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.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2024 ( Subtotal = $443,738 )
2024	2024	THE TRUSTEES OF MOUNT HOLYOKE COLLEGE	50 COLLEGE ST	SOUTH HADLEY	MA	01075	HAMPSHIRE	USA	Mental Health Research Grants	001	2	2/20/2024	COMPETING CONTINUATION	$399,365
2024	2024	THE TRUSTEES OF MOUNT HOLYOKE COLLEGE	50 COLLEGE ST	SOUTH HADLEY	MA	01075	HAMPSHIRE	USA	Mental Health Research Grants	002	2	6/11/2024	COMPETING CONTINUATION	$44,373
2024	2019	THE TRUSTEES OF MOUNT HOLYOKE COLLEGE	50 COLLEGE ST	SOUTH HADLEY	MA	01075	HAMPSHIRE	USA	Mental Health Research Grants	000	1	11/29/2023	NEW	$0
														Subtotal = $443,738

Issue Date FY: 2019 ( Subtotal = $453,807 )
2019	2019	TRUSTEES OF MOUNT HOLYOKE COLLEGE, THE	50 COLLEGE ST	SOUTH HADLEY	MA	01075	HAMPSHIRE	USA	Mental Health Research Grants	000	1	1/31/2019	NEW	$453,807
														Subtotal = $453,807

Grand Total All Awards = $897,545

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Maternal Interleukin-4 and allergic asthma in mouse offspring behavioral deficits

Award Number: R15MH119500

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 02/01/2019

PERIOD OF PERFORMANCE END DATE: 02/19/2027

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