• Tooka Aavani, Shadna A Rana, Richard Hawkes, and Quentin J Pittman.
• 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.
• Cerebellum. 2015 Oct 1; 14 (5): 491-505.

AbstractThere 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.

44 keywords...

hide…