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...

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Main Authors: Allman, B.L (Author), Baines, K.J (Author), De Oliveira, C. (Author), Doornaert, E.E (Author), Haddad, F.L (Author), Patel, S.V (Author), Renaud, S.J (Author), Schmid, S. (Author)
Format: Article
Language:English
Published: Elsevier Inc. 2022
Subjects:
Age
Online Access:View Fulltext in Publisher
LEADER 02843nam a2200337Ia 4500
001 10.1016-j.bbih.2022.100473
008 220718s2022 CNT 000 0 und d
020 |a 26663546 (ISSN) 
245 1 0 |a Interleukin 15 modulates the effects of poly I:C maternal immune activation on offspring behaviour 
260 0 |b Elsevier Inc.  |c 2022 
856 |z View Fulltext in Publisher  |u https://doi.org/10.1016/j.bbih.2022.100473 
520 3 |a 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. © 2022 The Authors 
650 0 4 |a Age 
650 0 4 |a Anxiety 
650 0 4 |a Autism spectrum disorder 
650 0 4 |a Interleukin 15 
650 0 4 |a Maternal immune activation 
650 0 4 |a Poly I:C 
650 0 4 |a Pregnancy 
650 0 4 |a Schizophrenia 
650 0 4 |a Social behaviour 
650 0 4 |a Startle 
700 1 |a Allman, B.L.  |e author 
700 1 |a Baines, K.J.  |e author 
700 1 |a De Oliveira, C.  |e author 
700 1 |a Doornaert, E.E.  |e author 
700 1 |a Haddad, F.L.  |e author 
700 1 |a Patel, S.V.  |e author 
700 1 |a Renaud, S.J.  |e author 
700 1 |a Schmid, S.  |e author 
773 |t Brain, Behavior, and Immunity - Health