University of Illinois Urbana-Champaign

From mother to offspring: tracking neurodevelopmental and behavioral consequences of gestational influenza

Kaushik, Arnav; Rigal, Fernando; Chalen, Izan; Antonson, Adrienne M

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https://hdl.handle.net/2142/132822

Description

Title
From mother to offspring: tracking neurodevelopmental and behavioral consequences of gestational influenza
Author(s)
  • Kaushik, Arnav
  • Rigal, Fernando
  • Chalen, Izan
  • Antonson, Adrienne M
Issue Date
2025-11-15
Keyword(s)
neurodevelopmental disorders
Date of Ingest
2026-02-22T16:50:28-06:00
Abstract
Maternal immune activation (MIA) is an established risk factor for neurodevelopmental disorders (NDDs) such as schizophrenia and autism spectrum disorder in offspring. In the US, about 63% of pregnant women experience at least one infection during pregnancy, nearly half of which are respiratory. This is important because maternal viral infections, such as influenza, can interfere with fetal brain development, potentially increasing the risk of NDDs by up to threefold. Most MIA studies employ pathogen mimetics like Poly(I:C). However, no study has shown the postnatal cortical and behavioral effects of gestational influenza A virus (IAV). To address this gap, we employed a translationally relevant model using a mouse-adapted H3N2 strain of IAV (X31), which engages both innate and adaptive immune responses. On gestational day 9.5, pregnant C57BL/6NTac dams were intranasally inoculated with IAV (X31; 10⁴ TCID₅₀) or a vehicle control (Saline). To separate the effects of prenatal insult from postnatal maternal care, pups were cross-fostered to lactating Swiss Webster dams at postnatal day (PD) 0.5. Cross-fostering was highly successful, with 17 of 18 litters adopted. Dams were monitored daily for weight gain. Dams were also scored post-inoculation for sickness behaviors, including ptosis, lethargy, huddling, eye/nose discharge, shivering, labored breathing, piloerection, and hunched posture. Compared to controls (n=12), X31-infected dams (n=15) showed weight loss beginning at 3 days post inoculation (dpi), resolving by 9 dpi (Time × Treatment p<0.0001, mixed-effects ANOVA). Sickness behavior scores were also significantly elevated (Time × Treatment p<0.0001, mixed-effects ANOVA) in X31 dams (n=13) versus controls (n=9), peaking at 2 and 3 dpi (p<0.0001, Šidák post-hoc test). At parturition, no group differences were observed in spleen weight (p=0.8446) or colon length (p=0.138), suggesting recovery from acute systemic effects observed earlier in infection (X31 n=13, Saline n=9; Mann-Whitney U test). Ongoing work will examine PD21 offspring brains for cortical excitatory neuron markers SATB2 and TBR1 to assess persistence of previously documented prenatal cortical disruptions. Behavioral assays modeling anxiety-like and repetitive behaviors, including marble burying, Y-Maze, open field, and elevated plus maze, are currently underway. All outcomes will be compared across sexes. Together, these novel findings will not only improve our understanding of the utility of live IAV infection as a clinically relevant MIA model, but also advance our understanding of how maternal influenza shapes offspring neurodevelopment and behavior.
Publisher
Society for Neuroscience
Series/Report Name or Number
Neuroscience 2025
Type of Resource
text
Genre of Resource
conference paper

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