The DOI matches its Crossref record; 43 of the 43 references it cites were found in a registry or an index.
Maternal Influenza Infection Causes Marked Behavioral and Pharmacological Changes in the Offspring
Open accessAbstract
Maternal viral infection is known to increase the risk for schizophrenia and autism in the offspring. Using this observation in an animal model, we find that respiratory infection of pregnant mice (both BALB/c and C57BL/6 strains) with the human influenza virus yields offspring that display highly abnormal behavioral responses as adults. As in schizophrenia and autism, these offspring display deficits in prepulse inhibition (PPI) in the acoustic startle response. Compared with control mice, the infected mice also display striking responses to the acute administration of antipsychotic (clozapine and chlorpromazine) and psychomimetic (ketamine) drugs. Moreover, these mice are deficient in exploratory behavior in both open-field and novel-object tests, and they are deficient in social interaction. At least some of these behavioral changes likely are attributable to the maternal immune response itself. That is, maternal injection of the synthetic double-stranded RNA polyinosinic-polycytidylic acid causes a PPI deficit in the offspring in the absence of virus. Therefore, maternal viral infection has a profound effect on the behavior of adult offspring, probably via an effect of the maternal immune response on the fetus.
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In the citing paper
“MIA models have ASD-like social, vocalization, ritualistic, exploration and other behavioral deficits [123–125].”
From The ASD Living Biology: from cell proliferation to clinical phenotype (2019) · cites this paper as [123]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“Altering the postnatal gut microbiota by early life treatment with the human gut bacterium Bacteroides fragilis sufficiently ameliorated deficits in the frequency and quality of adult ultrasonic vocalizations and reduced stereotypic burying behavior exhibited by the ASD-like mice.”
From Emerging Roles for the Gut Microbiome in Autism Spectrum Disorder (2017) · cites this paper as [31]
Experimental — accuracy not yet measuredIn the citing paper
“evidence from neuroanatomical, animal, and epidemiologic studies support the prenatal and early postnatal origins of autism.19–24”
From Environmental Chemical Exposures and Autism Spectrum Disorders: A Review of the Epidemiological Evidence (2014) · cites this paper as [23]
In the citing paper
“it has now been demonstrated through animal models that merely an activated immune response in the mother, absent any infection, is sufficient to lead to changes in the offspring”
From The Role of the Immune System in Autism Spectrum Disorder (2017) · cites this paper as Shi et al, 2003
In the citing paper
“Shi et al (2003) infected two strains of pregnant mice with human influenza virus and observed abnormal behavior, exploration, and social interaction in their offspring.”
From The Role of the Immune System in Autism Spectrum Disorder (2017) · cites this paper as Shi et al, 2003
In the citing paper
“the authors observed similar aberrant phenotypes in the same mice when using only poly(I:C) treatment rather than infection, suggesting that it was the maternal immune response rather than the infection itself that was responsible”
From The Role of the Immune System in Autism Spectrum Disorder (2017) · cites this paper as Shi et al, 2003
In the citing paper
“The consequences of MIA include behavioral deficits of broad relevance to ASD33, 34, 35”
From Maternal immune activation dysregulation of the fetal brain transcriptome and relevance to the pathophysiology of autism spectrum disorder (2018) · cites this paper as [33]
In the citing paper
“In a mouse model of maternal immune activation, a principal environmental risk factor for autism, mice develop core behavioral features of ASD (impaired social communication and stereotyped behaviors), as well as several neuropathologies and co-morbid gastrointestinal and immunological symptoms relevant to the human disorder (30–32).”
From Emerging Roles for the Gut Microbiome in Autism Spectrum Disorder (2017) · cites this paper as [31]
In the citing paper
“Similarly, mice and/or non-human primates that are exposed to maternal immune activation (MIA) through maternal infection with the viral mimetic, polyinosinic: polycitidylic acid (poly (I:C)), or maternal influenza infection, have offspring that develop abnormal social behaviors 646566, deficits in their immune profiles and anxiety-like phenotypes 67.”
From Gastrointestinal Issues and Autism Spectrum Disorder (2020) · cites this paper as [66]
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Metadata
- Authors
- Shi, L., Fatemi, S. H., Sidwell, R. W., & Patterson, P. H.
- Affiliations
- California Institute of Technology (US)
- University of Minnesota (US)
- Utah State University (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2003-01-01
- Volume
- 23
- Issue
- 1
- Pages
- 297-302
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6742135
- OpenAlex
- W2143217444
- Cited by
- 1,025
- References
- 43
- Citations by year
- 2026: 10 · 2025: 15 · 2024: 34 · 2023: 29 · 2022: 48 · 2021: 45 · 2020: 42 · 2019: 35 · 2018: 47 · 2017: 46 · 2016: 47 · 2015: 59 · 2014: 57 · 2013: 57 · 2012: 66
- FWCI
- 11.69
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neuroscience (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- CaltechAUTHORS (California Institute of Technology) (submittedVersion, cc-by)
- Funders
- National Alliance for Research on Schizophrenia and Depression
- National Institutes of Health (n01ai065291-009)
- National Institute of Allergy and Infectious Diseases (N01 AI 65291)
- Topics
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Maternal Mental Health During Pregnancy and Postpartum
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Keywords
- maternal influenza infection, prenatal viral infection, offspring behavior, prepulse inhibition, acoustic startle response, clozapine, chlorpromazine, ketamine, exploratory behavior, social interaction deficits, maternal immune response, polyinosinic-polycytidylic acid, schizophrenia, autism spectrum disorder, mouse strain differences
- MeSH terms
- Acoustic Stimulation, Animals, Animals, Newborn, Antiviral Agents, Anxiety, Behavior, Animal, Chlorpromazine, Clozapine, Exploratory Behavior, Female, Immunity, Ketamine, Mice, Inbred BALB C, Mice, Inbred C57BL, Motor Activity, Orthomyxoviridae Infections, Poly I-C, Pregnancy, Social Behavior, Antipsychotic Agents, Maternal-Fetal Relations, Mice
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