title: Maternal immune activation produces cerebellar hyperplasia and alterations in motor and social behaviors in male and female mice.
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.
authors: 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.
authors: Tooka
authors: T
authors: Aavani
authors: 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.
authors: Shadna A
authors: SA
authors: Rana
authors: 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.
authors: Richard
authors: R
authors: Hawkes
authors: 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. pittman@ucalgary.ca.
authors: Quentin J
authors: QJ
authors: Pittman
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D064026:Calbindins / Q000378:metabolism; D002531:Cerebellum / Q000002:abnormalities* / Q000254:growth & development / Q000378:metabolism* / Q000473:pathology; D002658:Developmental Disabilities / Q000209:etiology / Q000473:pathology; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D009069:Movement Disorders / Q000209:etiology*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009421:Nervous System Malformations / Q000209:etiology* / Q000473:pathology*; D011070:Poly I-C / Q000633:toxicity; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000276:immunology / Q000503:physiopathology*; D011597:Psychomotor Performance / Q000187:drug effects; D011689:Purkinje Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D012920:Social Behavior Disorders / Q000209:etiology*
chemical_list: D064026:Calbindins; D009419:Nerve Tissue Proteins; C071871:zebrin II; D011070:Poly I-C
keywords: Cerebellum; Development; Motor behavior; Poly(I:C); Purkinje cell; Zebrin