Maternal immune activation promotes hippocampal kindling epileptogenesis in mice.
http://www.ncbi.nlm.nih.gov/pubmed/23907982
OBJECTIVE:
Maternal immune activation (MIA) triggered by infections, has been identified as a cause of autism in the 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-6 and interleukin-1β was also addressed.
METHODS:
MIA was induced in C57BL/6 mice by polyinosinic-polycytidylic acid (PIC) injected during embryonic days 12-16. Beginning from postnatal day 40, the propensity of the offspring to epilepsy was examined using hippocampal kindling; autism-like behavior was studied using the sociability test. The involvement of interleukin-6 and interleukin-1β in PIC-induced effects was studied by the co-administration 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 interleukin-6 or interleukin-1β.
Neither of the recombinant cytokines alone increased the propensity to seizures; however when combined, they produced effects similar to the ones induced by PIC.
PIC- induced behavioral deficits were abolished by interleukin-6 antibodies and were mimicked by recombinant interleukin-6; interleukin-1β was not involved.
INTERPRETATION:
In addition to confirming previously established critical role of interleukin-6 in the development of autism-like behavior following MIA, the present study shows that concurrent involvement of interleukin-6 and interleukin-1β is required for priming the offspring for epilepsy. These data shed light on mechanisms of comorbidity between autism and epilepsy.
Copyright © 2013 American Neurological Association.
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Further Readings of Interest
http://en.wikipedia.org/wiki/Kindling_model
I am a mother of 2 boys with ASD. My husband is also on the spectrum. I have Systemic Lupus. Dx during last pregnancy. Husband has Hashimoto’s (his mother had an untreated case of HT too when pregnant with him.) I also run high titers of Epstein Barr when immune suppressed. Looking for connections between all of this. Incidentally, both boys had innocent heart murmers & we lost an infant with HLHS. Interested in any correlation with the heart/brain, etc. I have Anti-Sm cluster. No DS-DNA, but last two pregnancies had high proteinuria onset by 13 weeks (reversed.)
Elizabeth Dryden
drydendreams@gmail.com
autismcafe.org | extending the ASD sensory experience to neuro-typicals through creative art
Hi Elizabeth
Thank you for sharing some of your experiences. Have you thought of getting in contact with University of California MIND Institute ? I think a partnership with them could be valuable, based on what you have said.
regards
Thanks. I am in the mid-west, but I will delve further. Appreciate the response.
-Elizabeth