Maternal Influenza Viral Infection Causes Schizophrenia-Like Alterations of 5-HT 2A and mGlu 2 Receptors in the Adult Offspring
José L. Moreno, Mitsumasa Kurita, Terrell Holloway, Javier López, Richard Cadagan, Luis Martínez‐sobrido, Adolfo Garcı́a-sastre, Javier González-Maeso
Journal of Neuroscience February 2, 2011 DOI: 10.1523/jneurosci.4230-10.2011 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Mouse offspring of mothers infected with influenza A/WSN/33 (H1N1) virus |
| Intervention | maternal influenza viral infection |
| Topics | Serotonin |
| Keywords | Offspring Schizophrenia object-oriented programming Receptor Virology Pregnancy Genetics |
| Citations | 122 |
| Key findings | Maternal influenza infection in mice upregulates cortical 5-HT 2A receptors and downregulates mGlu 2 receptors, correlating with altered behavioral responses to hallucinogens and glutamate antipsychotics. |
Abstract
Epidemiological studies indicate that maternal influenza viral infection increases the risk for schizophrenia in the adult offspring. The serotonin and glutamate systems are suspected in the etiology of schizophrenia, as well as in the mechanism of action of antipsychotic drugs. The effects of hallucinogens, such as psilocybin and mescaline, require the serotonin 5-HT 2A receptor, and induce schizophrenia-like psychosis in humans. In addition, metabotropic glutamate receptor mGlu 2/3 agonists show promise as a new treatment for schizophrenia. Here, we investigated the level of expression and behavioral function of 5-HT 2A and mGlu 2 receptors in a mouse model of maternal influenza viral infection. We show that spontaneous locomotor activity is diminished by maternal infection with the mouse-adapted influenza A/WSN/33 (H1N1) virus. The behavioral responses to hallucinogens and glutamate antipsychotics are both affected by maternal exposure to influenza virus, with increased head-twitch response to hallucinogens and diminished antipsychotic-like effect of the glutamate agonist. In frontal cortex of mice born to influenza virus-infected mothers, the 5-HT 2A receptor is upregulated and the mGlu 2 receptor is downregulated, an alteration that may be involved in the behavioral changes observed. Additionally, we find that the cortical 5-HT 2A receptor-dependent signaling pathways are significantly altered in the offspring of infected mothers, showing higher c-fos , egr-1 , and egr-2 expression in response to the hallucinogenic drug DOI. Identifying a biochemical alteration that parallels the behavioral changes observed in a mouse model of prenatal viral infection may facilitate targeting therapies for treatment and prevention of schizophrenia.
Comparable studies
Other preclinical and animal studies on serotonin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo Mice | 2021 | Observational cohort | |
| Neurotoxicity of the psychedelic amphetamine, methylenedioxymethamphetamine. Rats (implied by typical neurochemical study context) | 1987 | Experimental study | |
| Psychedelics promote neuroplasticity through the activation of intracellular 5-HT2A receptors In vitro and in vivo (rodent) models | 2023 | Experimental study | |
| 3,4-Methylenedioxymethamphetamine and 3,4-methylenedioxyamphetamine destroy serotonin terminals in rat brain: quantification of neurodegeneration by measurement of [3H]paroxetine-labeled serotonin uptake sites. Rat brain | 1987 | Animal experiment | |
| Comparison of the monoamine transporters from human and mouse in their sensitivities to psychostimulant drugs Human and mouse dopamine, norepinephrine, and serotonin transporters expressed in cells | 2006 | In vitro laboratory study |
Citations in the library
Cited by 8
- Prenatal Stress Induces Schizophrenia-Like Alterations of Serotonin 2A and Metabotropic Glutamate 2 Receptors in the Adult Offspring: Role of Maternal Immune System Journal of Neuroscience January 16, 2013
- Serotonergic hallucinogens as translational models relevant to schizophrenia The International Journal of Neuropsychopharmacology August 13, 2013
- Fully automated head-twitch detection system for the study of 5-HT2A receptor pharmacology in vivo Scientific Reports October 3, 2019
- Long-lasting alterations in 5-HT2A receptor after a binge regimen of methamphetamine in mice The International Journal of Neuropsychopharmacology April 24, 2014
- Preclinical models of antipsychotic drug action The International Journal of Neuropsychopharmacology June 10, 2013
and 3 more in the library
Cites 10
- Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action Neuroreport December 1, 1998
- Reversal of Phencyclidine Effects by a Group II Metabotropic Glutamate Receptor Agonist in Rats Science August 28, 1998
- Serotonin research: contributions to understanding psychoses TIPS - Trends in Pharmacological Sciences August 1, 2008
- Transcriptome Fingerprints Distinguish Hallucinogenic and Nonhallucinogenic 5-Hydroxytryptamine 2A Receptor Agonist Effects in Mouse Somatosensory Cortex Journal of Neuroscience October 1, 2003
- EFFECTS OF MESCALINE AND LYSERGIC ACID (d-LSD-25) American Journal of Psychiatry February 1, 1952
and 5 more in the library