Stress in Puberty Unmasks Latent Neuropathological Consequences of Prenatal Immune Activation in Mice
Open accessAbstract
Double Whammy: Psychopathologies that cannot be explained by simple genetic or environmental circumstances may sometimes result from complex interplay between multiple inputs. Giovanoli et al. (p. 1095 ) analyzed the interactions between prenatal and postnatal stressors in mice to see what synergies give rise to psychopathologies in the adult mice. The results suggest that susceptibilities arise when mice are exposed to prenatal infection and also exposed to stressors around puberty. Stressors delivered later in adolescence did not seem to produce the same susceptibility. Although the mechanisms that impose the delay between stressors and psychopathology remain obscure, the timing and sequence of the triggers hint at possible cellular causes.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Prenatal exposure to polyinosinic:polycytidilic acid is a robust experimental model with well-characterized pathological and behavioral changes relevant to schizophrenia.
“In this regard, prenatal exposure to the immunostimulant polyinosinic:polycytidilic acid has been shown to represent a robust experimental model with a well-characterized evolution of pathologic and behavioural changes relevant to schizophrenia (Bitanihirwe et al., 2010; Giovanoli et al., 2013; Nyffeler et al., 2006; Richetto et al., 2013; Vuillermot et al., 2010)(Meyer, 2013).”
From Perineuronal nets and schizophrenia: The importance of neuronal coatings (2014) · cites this paper as Giovanoli et al., 2013
Antioxidant therapy with NAC reduces the pathological and behavioural consequences of maternal LPS treatment and reduces foetal proinflammatory cytokine production.
“Activated innate immune cells both produce and are activated by ROS: antioxidant therapy with NAC reduces the pathological and behavioural consequences of maternal LPS treatment and reduces foetal proinflammatory cytokine production 92,93 .”
From Linking early-life NMDAR hypofunction and oxidative stress in schizophrenia pathogenesis (2016) · cites this paper as [92]
Cites
Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2−ΔΔCT Method
Livak, K. J., & Schmittgen, T. D. (2001) · Methods · doi:10.1006/meth.2001.1262 · Cited by 180,860 · see citing works
Varese, F., Smeets, F., Drukker, M., Lieverse, R., Lataster, T., Viechtbauer, W., Read, J., van Os, J., & Bentall, R. P. (2012) · Schizophrenia Bulletin · doi:10.1093/schbul/sbs050 · Cited by 2,436 · see citing works
Microglial physiology: unique stimuli, specialized responses
Ransohoff, R. M., & Perry, V. H. (2009) · Annual Review of Immunology · doi:10.1146/annurev.immunol.021908.132528 · Cited by 1,858 · see citing works
Immune involvement in schizophrenia and autism: Etiology, pathology and animal models
Patterson, P. H. (2009) · Behavioural Brain Research · doi:10.1016/j.bbr.2008.12.016 · Cited by 766 · see citing works
Neural development, cell-cell signaling, and the “two-hit” hypothesis of schizophrenia
Maynard, T. M., Sikich, L., Lieberman, J. A., & LaMantia, A.-S. (2001) · Schizophrenia Bulletin · doi:10.1093/oxfordjournals.schbul.a006887 · Cited by 383 · see citing works
Schizophrenia and autism: both shared and disorder-specific pathogenesis via perinatal inflammation?
MEYER, U., FELDON, J., & DAMMANN, O. (2011) · Pediatric Research · doi:10.1203/pdr.0b013e318212c196 · Cited by 357 · see citing works
Self-citationHerbert, M. R. (2010) · Current Opinion in Neurology · doi:10.1097/wco.0b013e328336a01f · Cited by 356 · see citing works
Modeling an autism risk factor in mice leads to permanent immune dysregulation
Hsiao, E. Y., McBride, S. W., Chow, J., Mazmanian, S. K., & Patterson, P. H. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1202556109 · Cited by 340 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Host microbiota constantly control maturation and function of microglia in the CNS
Erny, D., Hrabě de Angelis, A. L., Jaitin, D., Wieghofer, P., Staszewski, O., David, E., Keren-Shaul, H., Mahlakoiv, T., Jakobshagen, K., Buch, T., et al. (2015) · Nature Neuroscience · doi:10.1038/nn.4030 · Cited by 3,569 · see citing works
Owen, M. J., Sawa, A., & Mortensen, P. B. (2016) · The Lancet · doi:10.1016/s0140-6736(15)01121-6 · Cited by 1,870 · see citing works
Self-citationMicroglia emerge as central players in brain disease
Salter, M. W., & Stevens, B. (2017) · Nature Medicine · doi:10.1038/nm.4397 · Cited by 1,767 · see citing works
Microglia Biology: One Century of Evolving Concepts
Prinz, M., Jung, S., & Priller, J. (2019) · Cell · doi:10.1016/j.cell.2019.08.053 · Cited by 1,525 · see citing works
Microglia and brain macrophages in the molecular age: from origin to neuropsychiatric disease
Prinz, M., & Priller, J. (2014) · Nature Reviews Neuroscience · doi:10.1038/nrn3722 · Cited by 1,329 · see citing works
Baumeister, D., Akhtar, R., Ciufolini, S., Pariante, C. M., & Mondelli, V (2016) · Molecular Psychiatry · doi:10.1038/mp.2015.67 · Cited by 1,084 · see citing works
Maternal immune activation and abnormal brain development across CNS disorders
Knuesel, I., Chicha, L., Britschgi, M., Schobel, S. A., Bodmer, M., Hellings, J. A., Toovey, S., & Prinssen, E. P. (2014) · Nature Reviews Neurology · doi:10.1038/nrneurol.2014.187 · Cited by 880 · see citing works
The Computational Anatomy of Psychosis
Adams, R. A., Stephan, K. E., Brown, H. R., Frith, C. D., & Friston, K. J. (2013) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2013.00047 · Cited by 850 · see citing works
“Or could there be another factor that reflects www.frontiersin.org May 2013 | Volume 4 | Article 47 | 21 the contribution of developmental and environmental stressors (Giovanoli et al., 2013) or a combination of the above.”
BackgroundMaternal immune activation and neuroinflammation in human neurodevelopmental disorders
Han, V. X., Patel, S., Jones, H. F., & Dale, R. C. (2021) · Nature Reviews Neurology · doi:10.1038/s41582-021-00530-8 · Cited by 683 · see citing works
Prenatal Poly(I:C) Exposure and Other Developmental Immune Activation Models in Rodent Systems
Meyer, U. (2014) · Biological Psychiatry · doi:10.1016/j.biopsych.2013.07.011 · Cited by 626 · see citing works
Self-citationImmune mediators in the brain and peripheral tissues in autism spectrum disorder
Estes, M. L., & McAllister, A. K. (2015) · Nature Reviews Neuroscience · doi:10.1038/nrn3978 · Cited by 514 · see citing works
Altering the course of schizophrenia: progress and perspectives
Millan, M. J., Andrieux, A., Bartzokis, G., Cadenhead, K., Dazzan, P., Fusar-Poli, P., Gallinat, J., Giedd, J., Grayson, D. R., Heinrichs, M., et al. (2016) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2016.28 · Cited by 516 · see citing works
Microglia Function in Central Nervous System Development and Plasticity
Schafer, D. P., & Stevens, B. (2015) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a020545 · Cited by 353 · see citing works
Steullet, P., Cabungcal, J.-H., Coyle, J., Didriksen, M., Gill, K., Grace, A. A., Hensch, T. K., LaMantia, A.-S., Lindemann, L., Maynard, T. M., et al. (2017) · Molecular Psychiatry · doi:10.1038/mp.2017.47 · Cited by 360 · see citing works
Self-citationMaternal immune activation and autism spectrum disorder: From rodents to nonhuman and human primates
Careaga, M., Murai, T., & Bauman, M. D. (2017) · Biological Psychiatry · doi:10.1016/j.biopsych.2016.10.020 · Cited by 348 · see citing works
Linking early-life NMDAR hypofunction and oxidative stress in schizophrenia pathogenesis
Hardingham, G. E., & Do, K. Q. (2016) · Nature Reviews Neuroscience · doi:10.1038/nrn.2015.19 · Cited by 304 · see citing works
Bauman, M. D., Iosif, A.-M., Smith, S. E. P., Bregere, C., Amaral, D. G., & Patterson, P. H. (2014) · Biological Psychiatry · doi:10.1016/j.biopsych.2013.06.025 · Cited by 294 · see citing works
Inflammation and the neural diathesis-stress hypothesis of schizophrenia: a reconceptualization
Howes, O. D., & McCutcheon, R. (2017) · Translational Psychiatry · doi:10.1038/tp.2016.278 · Cited by 288 · see citing works
Behavioral methods to study anxiety in rodents
Lezak, K. R., Missig, G., & Carlezon Jr, W. A. (2017) · Dialogues in Clinical Neuroscience · doi:10.31887/dcns.2017.19.2/wcarlezon · Cited by 290 · see citing works
Cross talk: the microbiota and neurodevelopmental disorders
Kelly, J. R., Minuto, C., Cryan, J. F., Clarke, G., & Dinan, T. G. (2017) · Frontiers in Neuroscience · doi:10.3389/fnins.2017.00490 · Cited by 271 · see citing works
Goeden, N., Velasquez, J., Arnold, K. A., Chan, Y., Lund, B. T., Anderson, G. M., & Bonnin, A. (2016) · The Journal of Neuroscience · doi:10.1523/jneurosci.2534-15.2016 · Cited by 264 · see citing works
Schork, A. J., Won, H., Appadurai, V., Nudel, R., Gandal, M., Delaneau, O., Revsbech Christiansen, M., Hougaard, D. M., Bækved-Hansen, M., Bybjerg-Grauholm, J., et al. (2019) · Nature Neuroscience · doi:10.1038/s41593-018-0320-0 · Cited by 223 · see citing works
Kępińska, A. P., Iyegbe, C. O., Vernon, A. C., Yolken, R., Murray, R. M., & Pollak, T. A. (2020) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2020.00072 · Cited by 193 · see citing works
Elevated Maternal C-Reactive Protein and Increased Risk of Schizophrenia in a National Birth Cohort
Canetta, S., Sourander, A., Surcel, H.-M., Hinkka-Yli-Salomäki, S., Leiviskä, J., Kellendonk, C., McKeague, I. W., & Brown, A. S. (2014) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2014.13121579 · Cited by 203 · see citing works
Juvenile Antioxidant Treatment Prevents Adult Deficits in a Developmental Model of Schizophrenia
Cabungcal, J.-H., Counotte, D. S., Lewis, E. M., Tejeda, H. A., Piantadosi, P., Pollock, C., Calhoon, G. G., Sullivan, E. M., Presgraves, E., Kil, J., et al. (2014) · Neuron · doi:10.1016/j.neuron.2014.07.028 · Cited by 204 · see citing works
Lombardo, M. V., Moon, H. M., Su, J., Palmer, T. D., Courchesne, E., & Pramparo, T. (2018) · Molecular Psychiatry · doi:10.1038/mp.2017.15 · Cited by 201 · see citing works
Schedlowski, M., Engler, H., & Grigoleit, J.-S. (2014) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2013.09.015 · Cited by 195 · see citing works
Self-citationHwang, Y., Kim, J., Shin, J.-Y., Kim, J.-I., Seo, J.-S., Webster, M. J., Lee, D., & Kim, S. (2013) · Translational Psychiatry · doi:10.1038/tp.2013.94 · Cited by 189 · see citing works
Baumeister, D., Ciufolini, S., & Mondelli, V. (2016) · Psychopharmacology · doi:10.1007/s00213-015-4044-5 · Cited by 183 · see citing works
Maternal immune activation in neurodevelopmental disorders
Solek, C. M., Farooqi, N., Verly, M., Lim, T. K., & Ruthazer, E. S. (2018) · Developmental Dynamics · doi:10.1002/dvdy.24612 · Cited by 168 · see citing works
Weber-Stadlbauer, U., Richetto, J., Labouesse, M. A., Bohacek, J., Mansuy, I. M., & Meyer, U. (2017) · Molecular Psychiatry · doi:10.1038/mp.2016.41 · Cited by 170 · see citing works
Self-citationMaternal immune activation in nonhuman primates alters social attention in juvenile offspring
Machado, C. J., Whitaker, A. M., Smith, S. E. P., Patterson, P. H., & Bauman, M. D. (2015) · Biological Psychiatry · doi:10.1016/j.biopsych.2014.07.035 · Cited by 136 · see citing works
Giovanoli, S., Notter, T., Richetto, J., Labouesse, M. A., Vuillermot, S., Riva, M. A., & Meyer, U. (2015) · Journal of Neuroinflammation · doi:10.1186/s12974-015-0437-y · Cited by 124 · see citing works
Self-citationPrinciples of inflammasome priming and inhibition: implications for psychiatric disorders
Herman, F. J., & Pasinetti, G. M. (2018) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2018.06.010 · Cited by 115 · see citing works
Prata, J., Santos, S. G., Almeida, M. I., Coelho, R., & Barbosa, M. A. (2017) · Journal of Neuroinflammation · doi:10.1186/s12974-017-0938-y · Cited by 115 · see citing works
Perineuronal nets and schizophrenia: The importance of neuronal coatings
Bitanihirwe, B. K. Y., & Woo, T.-U. W. (2014) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2014.03.018 · Cited by 95 · see citing works
Kirsten, T. B., Queiroz-Hazarbassanov, N., Bernardi, M. M., & Felicio, L. F. (2015) · Life Sciences · doi:10.1016/j.lfs.2015.02.027 · Cited by 83 · see citing works
Kirsten, T. B., Chaves-Kirsten, G. P., Bernardes, S., Scavone, C., Sarkis, J. E., Bernardi, M. M., & Felicio, L. F. (2015) · PLOS ONE · doi:10.1371/journal.pone.0134565 · Cited by 65 · see citing works
Straley, M. E., Van Oeffelen, W., Theze, S., Sullivan, A. M., O’Mahony, S. M., Cryan, J. F., & O’Keeffe, G. W. (2017) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2016.06.002 · Cited by 52 · see citing works
Microglia and Sensitive Periods in Brain Development
Dziabis, J. E., & Bilbo, S. D. (2021) · Current Topics in Behavioral Neurosciences · doi:10.1007/7854_2021_242 · Cited by 42 · see citing works
Comorbidity of mental and physical disorders
(2014) · Key Issues in Mental Health · doi:10.1159/isbn.978-3-318-02604-7 · Cited by 37 · see citing works
Tan, T., Wang, W., Williams, J., Ma, K., Cao, Q., & Yan, Z. (2019) · Schizophrenia Bulletin · doi:10.1093/schbul/sby163 · Cited by 29 · see citing works
Turner, K. M., & Burne, T. H. J. (2013) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2013.00097 · Cited by 16 · see citing works
“Future studies could take a number of directions, including the use of GxG and ExE studies to identify the influence of genetic and environmental factors; as well as understanding the mechanisms that lead to increased vulnerability (Giovanoli et al., 2013).”
BackgroundBates, V., Maharjan, A., Millar, J., Bilkey, D. K., & Ward, R. D. (2018) · Behavioral Neuroscience · doi:10.1037/bne0000230 · Cited by 15 · see citing works
- Authors
- Giovanoli, S., Engler, H., Engler, A., Richetto, J., Voget, M., Willi, R., Winter, C., Riva, M. A., Mortensen, P. B., Feldon, J., Schedlowski, M., & Meyer, U.
- Affiliations
- ETH Zurich (CH)
- Essen University Hospital (DE)
- University of Milan (IT)
- Technische Universität Dresden (DE)
- F. Hoffmann-La Roche AG (CH)
- Aarhus University (DK)
- Corresponding author
- Meyer, Urs
- ORCID
- Venue
- Science
- Published
- 2013-03
- Volume
- 339
- Issue
- 6123
- Pages
- 1095-1099
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2072878021
- Cited by
- 459
- References
- 8
- Citations by year
- 2026: 9 · 2025: 14 · 2024: 22 · 2023: 26 · 2022: 29 · 2021: 38 · 2020: 35 · 2019: 36 · 2018: 44 · 2017: 34 · 2016: 43 · 2015: 51 · 2014: 40 · 2013: 37
- FWCI
- 25.70
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- other-oa
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Archivio Istituzionale della Ricerca (Universita Degli Studi Di Milano) (submittedVersion, other-oa)
- Funders
- F. Hoffmann-La Roche
- Stanley Medical Research Institute
- European Commission (FP7/2007-2011, FP7/2007, 259679)
- Deutsche Forschungsgemeinschaft (FOR 1581)
- Lundbeckfonden
- Türkiye Bilimler Akademisi
- Hacettepe Üniversitesi
- H. Lundbeck A/S
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- 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
- Keywords
- prenatal immune activation, puberty, neuropsychiatric disorders, brain immune response, neuroinflammation, mouse model, neurochemistry
- MeSH terms
- Animals, Mental Disorders, Disease Models, Animal, Female, Humans, Mice, Inbred C57BL, Poly I-C, Pregnancy, Prenatal Exposure Delayed Effects, Puberty, Stress, Physiological, Cytokines, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
