Interleukin 15 modulates the effects of poly I:C maternal immune activation on offspring behaviour
Maternal infections during pregnancy are linked with an increased risk for disorders like Autism Spectrum Disorder and schizophrenia in the offspring. Although precise mechanisms are still unclear, clinical and preclinical evidence suggest a strong role for maternal immune activation (MIA) in the ne...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-08-01
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| Series: | Brain, Behavior, & Immunity - Health |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666354622000631 |
| _version_ | 1811219190463332352 |
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| author | Faraj L. Haddad Salonee V. Patel Ella E. Doornaert Cleusa De Oliveira Brian L. Allman Kelly J. Baines Stephen J. Renaud Susanne Schmid |
| author_facet | Faraj L. Haddad Salonee V. Patel Ella E. Doornaert Cleusa De Oliveira Brian L. Allman Kelly J. Baines Stephen J. Renaud Susanne Schmid |
| author_sort | Faraj L. Haddad |
| collection | DOAJ |
| description | Maternal infections during pregnancy are linked with an increased risk for disorders like Autism Spectrum Disorder and schizophrenia in the offspring. Although precise mechanisms are still unclear, clinical and preclinical evidence suggest a strong role for maternal immune activation (MIA) in the neurodevelopmental disruptions caused by maternal infection. Previously, studies using the Polyinosinic:Polycytidylic (Poly I:C) MIA preclinical model showed that cytokines like Interleukin 6 (Il6) are important mediators of MIA's effects. In this study, we hypothesized that Il15 may similarly act as a mediator of Poly I:C MIA, given its role in the antiviral immune response. To test this hypothesis, we induced Poly I:C MIA at gestational day 9.5 in wildtype (WT) and Il15−/− rat dams and tested their offspring in adolescence and adulthood. Poly I:C MIA and Il15 knockout produced both independent and synergistic effects on offspring behaviour. Poly I:C MIA decreased startle reactivity in adult WT offspring but resulted in increased adolescent anxiety and decreased adult locomotor activity in Il15−/− offspring. In addition, Poly I:C MIA led to genotype-independent effects on locomotor activity and prepulse inhibition. Finally, we showed that Il15−/− offspring exhibit distinct phenotypes that were unrelated to Poly I:C MIA including altered startle reactivity, locomotion and signal transduction in the auditory brainstem. Overall, our findings indicate that the lack of Il15 can leave offspring either more or less susceptible to Poly I:C MIA, depending on the phenotype in question. Future studies should examine the contribution of fetal versus maternal Il15 in MIA to determine the precise developmental mechanisms underlying these changes. |
| first_indexed | 2024-04-12T07:22:25Z |
| format | Article |
| id | doaj.art-256e1779876f47988ad31827df9f7c3a |
| institution | Directory Open Access Journal |
| issn | 2666-3546 |
| language | English |
| last_indexed | 2024-04-12T07:22:25Z |
| publishDate | 2022-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Brain, Behavior, & Immunity - Health |
| spelling | doaj.art-256e1779876f47988ad31827df9f7c3a2022-12-22T03:42:17ZengElsevierBrain, Behavior, & Immunity - Health2666-35462022-08-0123100473Interleukin 15 modulates the effects of poly I:C maternal immune activation on offspring behaviourFaraj L. Haddad0Salonee V. Patel1Ella E. Doornaert2Cleusa De Oliveira3Brian L. Allman4Kelly J. Baines5Stephen J. Renaud6Susanne Schmid7Anatomy & Cell Biology, Schulich School of Medicine & Dentistry, CanadaAnatomy & Cell Biology, Schulich School of Medicine & Dentistry, CanadaAnatomy & Cell Biology, Schulich School of Medicine & Dentistry, CanadaAnatomy & Cell Biology, Schulich School of Medicine & Dentistry, CanadaAnatomy & Cell Biology, Schulich School of Medicine & Dentistry, CanadaAnatomy & Cell Biology, Schulich School of Medicine & Dentistry, CanadaAnatomy & Cell Biology, Schulich School of Medicine & Dentistry, CanadaAnatomy & Cell Biology, Schulich School of Medicine & Dentistry, Canada; Department of Psychology, The University of Western Ontario, ON, Canada; Corresponding author. Anatomy & Cell Biology, Schulich School of Medicine & Dentistry, 1151 Richmond Street, London, ON, N6A 3K7, Canada.Maternal infections during pregnancy are linked with an increased risk for disorders like Autism Spectrum Disorder and schizophrenia in the offspring. Although precise mechanisms are still unclear, clinical and preclinical evidence suggest a strong role for maternal immune activation (MIA) in the neurodevelopmental disruptions caused by maternal infection. Previously, studies using the Polyinosinic:Polycytidylic (Poly I:C) MIA preclinical model showed that cytokines like Interleukin 6 (Il6) are important mediators of MIA's effects. In this study, we hypothesized that Il15 may similarly act as a mediator of Poly I:C MIA, given its role in the antiviral immune response. To test this hypothesis, we induced Poly I:C MIA at gestational day 9.5 in wildtype (WT) and Il15−/− rat dams and tested their offspring in adolescence and adulthood. Poly I:C MIA and Il15 knockout produced both independent and synergistic effects on offspring behaviour. Poly I:C MIA decreased startle reactivity in adult WT offspring but resulted in increased adolescent anxiety and decreased adult locomotor activity in Il15−/− offspring. In addition, Poly I:C MIA led to genotype-independent effects on locomotor activity and prepulse inhibition. Finally, we showed that Il15−/− offspring exhibit distinct phenotypes that were unrelated to Poly I:C MIA including altered startle reactivity, locomotion and signal transduction in the auditory brainstem. Overall, our findings indicate that the lack of Il15 can leave offspring either more or less susceptible to Poly I:C MIA, depending on the phenotype in question. Future studies should examine the contribution of fetal versus maternal Il15 in MIA to determine the precise developmental mechanisms underlying these changes.http://www.sciencedirect.com/science/article/pii/S2666354622000631Maternal immune activationPregnancyPoly I:CInterleukin 15StartleAutism spectrum disorder |
| spellingShingle | Faraj L. Haddad Salonee V. Patel Ella E. Doornaert Cleusa De Oliveira Brian L. Allman Kelly J. Baines Stephen J. Renaud Susanne Schmid Interleukin 15 modulates the effects of poly I:C maternal immune activation on offspring behaviour Brain, Behavior, & Immunity - Health Maternal immune activation Pregnancy Poly I:C Interleukin 15 Startle Autism spectrum disorder |
| title | Interleukin 15 modulates the effects of poly I:C maternal immune activation on offspring behaviour |
| title_full | Interleukin 15 modulates the effects of poly I:C maternal immune activation on offspring behaviour |
| title_fullStr | Interleukin 15 modulates the effects of poly I:C maternal immune activation on offspring behaviour |
| title_full_unstemmed | Interleukin 15 modulates the effects of poly I:C maternal immune activation on offspring behaviour |
| title_short | Interleukin 15 modulates the effects of poly I:C maternal immune activation on offspring behaviour |
| title_sort | interleukin 15 modulates the effects of poly i c maternal immune activation on offspring behaviour |
| topic | Maternal immune activation Pregnancy Poly I:C Interleukin 15 Startle Autism spectrum disorder |
| url | http://www.sciencedirect.com/science/article/pii/S2666354622000631 |
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