title: Maternal immune activation promotes hippocampal kindling epileptogenesis in mice.
abstract: OBJECTIVE
  Maternal immune activation (MIA) triggered by infections has been identified as a cause of autism in offspring. Considering the involvement of perturbations in innate immunity in epilepsy, we examined whether MIA represents a risk factor for epilepsy as well. The role of specific MIA components interleukin (IL)-6 and IL-1β was also addressed.
  
  
  METHODS
  MIA was induced in C57BL/6 mice by polyinosinic-polycytidylic acid (PIC) injected during embryonic days 12 to 16. Beginning from postnatal day 40, the propensity of the offspring to epilepsy was examined using hippocampal kindling; autismlike behavior was studied using the sociability test. The involvement of IL-6 and IL-1β in PIC-induced effects was studied by the coadministration of the cytokine antibodies with PIC, and by delivering recombinant cytokines in lieu of PIC.
  
  
  RESULTS
  The offspring of PIC-exposed mice exhibited increased hippocampal excitability, accelerated kindling rate, prolonged increase of seizure susceptibility after kindling, and diminished sociability. Epileptic impairments were abolished by antibodies to IL-6 or IL-1β. Neither of the recombinant cytokines alone increased the propensity to seizures; however, when combined, they produced effects similar to those induced by PIC. PIC-induced behavioral deficits were abolished by IL-6 antibodies and were mimicked by recombinant IL-6; IL-1β was not involved.
  
  
  CONCLUSIONS
  In addition to confirming the previously established critical role of IL-6 in the development of autismlike behavior following MIA, the present study shows that concurrent involvement of IL-6 and IL-1β is required for priming the offspring for epilepsy. These data shed light on mechanisms of comorbidity between autism and epilepsy.
authors.affiliation: Department of Pediatrics, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Pineda
authors.forename: Don
authors.initials: D
authors.lastname: Shin
authors.forename: Su Jeong
authors.initials: SJ
authors.lastname: You
authors.forename: Stéphane
authors.initials: S
authors.lastname: Auvin
authors.forename: Raman
authors.initials: R
authors.lastname: Sankar
authors.forename: Andréy
authors.initials: A
authors.lastname: Mazarati
mesh_terms: D000818:Animals; D000906:Antibodies / Q000008:administration & dosage; D001831:Body Temperature / Q000187:drug effects; D004827:Epilepsy / Q000188:drug therapy / Q000209:etiology*; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology*; D007369:Interferon Inducers / Q000633:toxicity; D053583:Interleukin-1beta / Q000097:blood / Q000276:immunology; D015850:Interleukin-6 / Q000097:blood / Q000276:immunology; D007696:Kindling, Neurologic / Q000187:drug effects / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011070:Poly I-C / Q000633:toxicity; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced / Q000276:immunology* / Q000503:physiopathology*; D012919:Social Behavior
chemical_list: D000906:Antibodies; D007369:Interferon Inducers; D053583:Interleukin-1beta; D015850:Interleukin-6; D011070:Poly I-C
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