Gestational flu exposure induces changes in neurochemicals, affiliative hormones and brainstem inflammation, in addition to autism-like behaviors in mice
Abstract
The prevalence of neurodevelopmental disorders such as autism is increasing, however the etiology of these disorders is unclear and thought to involve a combination of genetic, environmental and immune factors. A recent epidemiological study found that gestational viral exposure during the first trimester increases risk of autism in offspring by twofold. In mice gestational viral exposures alter behavior of offspring, but the biological mechanisms which underpin these behavioral changes are unclear. We hypothesized that gestational viral exposure induces changes in affiliative hormones, brainstem autonomic nuclei and neurotransmitters which are associated with behavioral alterations in offspring. To address this hypothesis, we exposed pregnant mice to influenza A virus (H3N2) on gestational day 9 and determined behavioral, hormonal and brainstem changes in male and female offspring. We found that gestational flu exposure induced dose-dependent alterations in social and aggressive behaviors (p≤0.05) in male and female offspring and increases in locomotor behaviors particularly in male offspring (p≤0.05). We found that flu exposure was also associated with reductions in oxytocin and serotonin (p≤0.05) levels in male and female offspring and sex-specific changes in dopamine metabolism. In addition we found changes in catecholaminergic and microglia density in brainstem tissues of male flu exposed offspring only (p≤0.05). This study demonstrates that gestational viral exposure induces behavioral changes in mice, which are associated with alterations in affiliative hormones. In addition we found sex-specific changes in locomotor behavior, which may be associated with sex-specific alterations in dopamine metabolism and brainstem inflammation. Further investigations into maternal immune responses are necessary to unravel the molecular mechanisms which underpin abnormal hormonal, immune and behavioral responses in offspring after gestational viral exposure.
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Prenatal influenza A virus exposure in male mouse offspring increased home-cage locomotor behavior measured by videography.
“a second study observed increased locomotor behaviors in their home cage as documented via coding of videography in male mice offspring exposed to the influenza A virus during gestation (Miller et al., 2013).”
From Neuroinflammation as a risk factor for attention deficit hyperactivity disorder (2019) · cites this paper as Miller et al., 2013
Prenatal flu exposure reduced serum 5-HT levels particularly in male offspring and increased 5-HT metabolism in female offspring.
“Prenatal exposure to the flu in a mouse model also reduced serum 5-HT levels, particularly in the male offspring, and increased 5-HT metabolism in female offspring (Miller et al., 2013).”
From Neuroinflammation as a risk factor for attention deficit hyperactivity disorder (2019) · cites this paper as Miller et al., 2013
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- Authors
- Miller, V. M., Zhu, Y., Bucher, C., McGinnis, W., Ryan, L. K., Siegel, A., & Zalcman, S.
- Affiliations
- New York State Department of Health (US)
- Rutgers New Jersey Medical School (US)
- State University of New York (US)
- Autism Research Institute (US)
- Corresponding author
- Miller, V.M.
- ORCID
- Ryan, L.K.
- Venue
- Brain, Behavior, and Immunity
- Publisher
- Elsevier BV
- Published
- 2013-10
- Volume
- 33
- Pages
- 153-163
- ISSN
- 0889-1591 (ISSN-L)
- OpenAlex
- W2060753137
- Cited by
- 36
- References
- 9
- Citations by year
- 2025: 3 · 2023: 1 · 2022: 9 · 2021: 1 · 2020: 2 · 2019: 3 · 2018: 5 · 2017: 2 · 2016: 1 · 2015: 5 · 2014: 3 · 2013: 1
- FWCI
- 4.99
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Brain Behavior and Immunity (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- H3N2, autism-like behavior, social behavior, aggression, locomotor behavior, oxytocin, serotonin, dopamine metabolism, brainstem inflammation, catecholaminergic neurons, microglia, sex differences, maternal immune activation, neurodevelopmental disorders
- MeSH terms
- Animals, Autistic Disorder, Blood Glucose, Body Weight, Brain Stem, Chromatography, High Pressure Liquid, Female, Inflammation, Male, Mice, Inbred BALB C, Motor Activity, Orthomyxoviridae Infections, Oxytocin, Pilot Projects, Pregnancy, Random Allocation, Stereotyped Behavior, Testosterone, Maternal Exposure, Mice, Influenza A Virus, H3N2 Subtype
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