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Maternal Immune Activation Produces Cerebellar Hyperplasia and Alterations in Motor and Social Behaviors in Male and Female Mice

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Abstract

There have been suggestions that maternal immune activation is associated with alterations in motor behavior in offspring. To explore this further, we treated pregnant mice with polyinosinic:polycytidylic acid (poly(I:C)), a viral mimetic that activates the innate immune system, or saline on embryonic days 13–15. At postnatal day (P) 18, offspring cerebella were collected from perfused brains and immunostained as whole-mounts for zebrin II. Measurements of zebrin II+/− stripes in both sexes indicated that prenatal poly(I:C)-exposed offspring had significantly wider stripes; this difference was also seen in similarly treated offspring in adulthood (~P120). When sagittal sections of the cerebellum were immunostained for calbindin and Purkinje cell numbers were counted, we observed greater numbers of Purkinje cells in poly(I:C) offspring at both P18 and ~ P120. In adolescence (~P40), both male and female prenatal poly(I:C)-exposed offspring exhibited poorer performance on the rotarod and ladder rung tests; deficits in performance on the latter test persisted into adulthood. Offspring of both sexes from poly(I:C) dams also exhibited impaired social interaction in adolescence, but this difference was no longer apparent in adulthood. Our results suggest that maternal immune exposure at a critical time of cerebellum development can enhance neuronal survival or impair normal programmed cell death of Purkinje cells, with lasting consequences on cerebellar morphology and a variety of motor and non-motor behaviors.

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Acknowledgments

This work was supported by Canadian Institutes of Health Research grants to RH and QJP. SAR and QJP were supported by personnel awards from Alberta Innovates - Health Solutions. We thank Dr. Mio Tsutsui for valuable technical support and the RUN facility of the Hotchkiss Brain Institute for access to behavioral facilities.

Disclosure of Potential Conflicts of Interest

The authors declare no conflicts of interest either directly or indirectly related to this research. This research was funded by the Canadian Institutes of Health Research (MOP 191318).

Research Involving Animals

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the University of Calgary where the research was performed and were approved by the University of Calgary Animal Care Committee in accordance with guidelines from the Canadian Council on Animal Care.

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  1. Department of Physiology and Pharmacology, Hotchkiss Brain Institute, Cumming School of Medicine, Health Sciences Centre, University of Calgary, 3330 Hospital Drive NW, Calgary, T2N 4N1, Alberta, Canada

    Tooka Aavani, Shadna A. Rana & Quentin J. Pittman

  2. Department of Cell Biology & Anatomy, Genes & Development Research Group, Hotchkiss Brain Institute, Cumming School of Medicine, Health Sciences Centre, University of Calgary, 3330 Hospital Drive NW, Calgary, Alberta, T2N 4N1, Canada

    Richard Hawkes

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  1. Tooka Aavani
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Correspondence to Quentin J. Pittman.

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Tooka Aavani and Shadna A. Rana are co-first authors.

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Aavani, T., Rana, S.A., Hawkes, R. et al. Maternal Immune Activation Produces Cerebellar Hyperplasia and Alterations in Motor and Social Behaviors in Male and Female Mice. Cerebellum 14, 491–505 (2015). https://doi.org/10.1007/s12311-015-0669-5

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