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Conference Paper: Effects of interleukin-6 on neuronal development in an in vitro maternal immune activation model

TitleEffects of interleukin-6 on neuronal development in an in vitro maternal immune activation model
Authors
Issue Date2010
PublisherSociety for Neuroscience.
Citation
The 40th Annual Meeting of the Society for Neuroscience (SfN 2010), San Diego, CA., 13-17 November 2010. How to Cite?
AbstractAutism is a complex neurodevelopmental disorder. While genetic and environmental factors play key roles in the pathogenesis, epidemiological evidence strongly suggests that maternal infection during pregnancy may contribute to an increased risk of the disorder for the offspring. It is believed that the imbalance of pro-inflammatory cytokines, such as interleukin-6 (IL-6), disrupt prenatal or early postnatal brain development, and subsequently lead to behavioural changes in the child. To better understand how IL-6 modulates neurodevelopment, primary cortical cultures were prepared from wild-type fetal mice at 15-16 days gestation. On day 7 in vitro, cultures were treated with IL-6 for 24 hours (0pg/mL to 2000pg/mL). Cell viability and survival were assessed by MTT and LDH assays, respectively. The expressions of inducible nitric oxide synthase (iNOS), neuronal nitric oxide synthase (nNOS), and phospho-tau were examined by Western blot. Compared to the control group, cortical cultures exposed to 10pg/mL IL-6 did not show any difference in survival. However, cell viability started to decrease at 100pg/mL, and at the concentrations of 1000 pg/mL and 2000 pg/mL, 50% reduction in viability was noted (P<0.01 vs. control). Likewise, IL-6 challenge at 100pg/mL and 1000pg/mL significantly increased the release of LDH (P<0.01 vs. control). The expression of iNOS was significantly increased at 100pg/mL and 1000pg/mL (P<0.01 vs. control). Interestingly, nNOS and phospho-tau expressions showed opposite biphasic responses with increasing IL-6 doses (P<0.01 vs. control). These preliminary data suggest that the rise in IL-6 during pregnancy may disrupt fetal neuronal development by increasing the iNOS-mediated production of nitric oxide (NO), decreasing nNOS-mediated NO release, and interfering with microtubule assembly. Further experiments to confirm these findings and explore the underlying mechanisms are in progress.
DescriptionPoster Session 870. Developmental Disorders: Animal Models and Mechanisms: no. 870.18/BB10
Persistent Identifierhttp://hdl.handle.net/10722/136009

 

DC FieldValueLanguage
dc.contributor.authorLee, CFKen_US
dc.contributor.authorMcAlonan, GM-
dc.contributor.authorLaw, ACK-
dc.date.accessioned2011-07-27T02:01:36Z-
dc.date.available2011-07-27T02:01:36Z-
dc.date.issued2010en_US
dc.identifier.citationThe 40th Annual Meeting of the Society for Neuroscience (SfN 2010), San Diego, CA., 13-17 November 2010.en_US
dc.identifier.urihttp://hdl.handle.net/10722/136009-
dc.descriptionPoster Session 870. Developmental Disorders: Animal Models and Mechanisms: no. 870.18/BB10-
dc.description.abstractAutism is a complex neurodevelopmental disorder. While genetic and environmental factors play key roles in the pathogenesis, epidemiological evidence strongly suggests that maternal infection during pregnancy may contribute to an increased risk of the disorder for the offspring. It is believed that the imbalance of pro-inflammatory cytokines, such as interleukin-6 (IL-6), disrupt prenatal or early postnatal brain development, and subsequently lead to behavioural changes in the child. To better understand how IL-6 modulates neurodevelopment, primary cortical cultures were prepared from wild-type fetal mice at 15-16 days gestation. On day 7 in vitro, cultures were treated with IL-6 for 24 hours (0pg/mL to 2000pg/mL). Cell viability and survival were assessed by MTT and LDH assays, respectively. The expressions of inducible nitric oxide synthase (iNOS), neuronal nitric oxide synthase (nNOS), and phospho-tau were examined by Western blot. Compared to the control group, cortical cultures exposed to 10pg/mL IL-6 did not show any difference in survival. However, cell viability started to decrease at 100pg/mL, and at the concentrations of 1000 pg/mL and 2000 pg/mL, 50% reduction in viability was noted (P<0.01 vs. control). Likewise, IL-6 challenge at 100pg/mL and 1000pg/mL significantly increased the release of LDH (P<0.01 vs. control). The expression of iNOS was significantly increased at 100pg/mL and 1000pg/mL (P<0.01 vs. control). Interestingly, nNOS and phospho-tau expressions showed opposite biphasic responses with increasing IL-6 doses (P<0.01 vs. control). These preliminary data suggest that the rise in IL-6 during pregnancy may disrupt fetal neuronal development by increasing the iNOS-mediated production of nitric oxide (NO), decreasing nNOS-mediated NO release, and interfering with microtubule assembly. Further experiments to confirm these findings and explore the underlying mechanisms are in progress.-
dc.languageengen_US
dc.publisherSociety for Neuroscience.-
dc.relation.ispartofAnnual Meeting of the Society for Neuroscience, SfN 2010en_US
dc.rights40th Annual Meeting of the Society for Neuroscience, SfN 2010. Copyright © Society for Neuroscience.-
dc.titleEffects of interleukin-6 on neuronal development in an in vitro maternal immune activation modelen_US
dc.typeConference_Paperen_US
dc.identifier.emailMcAlonan, GM: mcalonan@hkucc.hku.hken_US
dc.identifier.emailLaw, ACK: acklaw@hku.hk-
dc.identifier.authorityMcAlonan, GM=rp00475en_US
dc.description.naturelink_to_OA_fulltext-
dc.identifier.hkuros187364en_US
dc.publisher.placeUnited States-

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