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Ann Neurol. 2013 Jul;74(1):11-9. doi: 10.1002/ana.23898. Epub 2013 Aug 6.

Maternal immune activation promotes hippocampal kindling epileptogenesis in mice.

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Department of Pediatrics, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA.



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.


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.


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.


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.

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