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Nrg1 mutation alters cytokine responses relevant to schizophrenia

Conference Paper


Abstract


  • Purpose: Gene-immune interactions are hypothesised to contribute to

    schizophrenia disease development. With Neureulin-1 (Nrg1) a candidate

    vulnerability gene and altered cytokines levels recently reported in

    human Nrg1 mutants; we investigated the peripheral and central cytokine

    response of Nrg1 heterozygous mutant (Nrg1-Het) mice following an

    immune stimulus. Methods: We treated adult Nrg1-Het and wild type

    littermates (WT) with melanoma cells, established to induce a chronic

    immune response, for 9 days (n>8 per group). Cytokine levels were

    measured in the plasma (n>6 per group) and the brain (n>3 per group)

    using Luminex or Western blot. Gene expression of signalling molecules

    was measured using RT-qPCR (n>3 per group). Significance accepted

    at p<0.05. Results: We found higher plasma G-CSF and IL-6 levels in

    Nrg1-Het immune challenged compared to WT challenged mice. Lower

    levels of G-CSF were found in the hippocampus of challenged Nrg1-Het

    compared to WT mice. Further, 55% lower IL-6 was found in the prefrontal

    cortex of Nrg1-Het challenged compared to Nrg1-Het unchallenged mice.

    In unchallenged mice, Nrg1-Hets had lower levels of phosphorylated AKT

    protein in the hippocampus. Further, AKT1 mRNA expression was lower

    in the prefrontal cortex while SOCS3 mRNA expression was higher in

    Nrg1-Het mice compared to WT. In immune challenged animals, JAK1

    mRNA expression was lower in the hippocampus of Nrg1-Het compared

    to WT mice. Conclusion: This study demonstrates that Nrg1 mutation

    alters IL-6 and G-CSF in the periphery and the brain following an immune

    challenge. It further shows alterations in AKT, SOCS3 and JAK1 in the

    brain, key shared signalling pathway molecules. Together these data

    indicate interactions between Nrg1 mutation and immune challenge

    can affect signalling, which may alter neuronal activity in schizophreniarelevant

    brain areas.

Publication Date


  • 2013

Citation


  • Snikeris, P., Huang, X. -F. & Frank, E. (2013). Nrg1 mutation alters cytokine responses relevant to schizophrenia. 33rd Meeting of the Australian Neuroscience Society: Program, Abstracts & List of Registrants (pp. 160-160). Australia: ANS.

Ro Metadata Url


  • http://ro.uow.edu.au/smhpapers/908

Start Page


  • 160

End Page


  • 160

Place Of Publication


  • Australia

Abstract


  • Purpose: Gene-immune interactions are hypothesised to contribute to

    schizophrenia disease development. With Neureulin-1 (Nrg1) a candidate

    vulnerability gene and altered cytokines levels recently reported in

    human Nrg1 mutants; we investigated the peripheral and central cytokine

    response of Nrg1 heterozygous mutant (Nrg1-Het) mice following an

    immune stimulus. Methods: We treated adult Nrg1-Het and wild type

    littermates (WT) with melanoma cells, established to induce a chronic

    immune response, for 9 days (n>8 per group). Cytokine levels were

    measured in the plasma (n>6 per group) and the brain (n>3 per group)

    using Luminex or Western blot. Gene expression of signalling molecules

    was measured using RT-qPCR (n>3 per group). Significance accepted

    at p<0.05. Results: We found higher plasma G-CSF and IL-6 levels in

    Nrg1-Het immune challenged compared to WT challenged mice. Lower

    levels of G-CSF were found in the hippocampus of challenged Nrg1-Het

    compared to WT mice. Further, 55% lower IL-6 was found in the prefrontal

    cortex of Nrg1-Het challenged compared to Nrg1-Het unchallenged mice.

    In unchallenged mice, Nrg1-Hets had lower levels of phosphorylated AKT

    protein in the hippocampus. Further, AKT1 mRNA expression was lower

    in the prefrontal cortex while SOCS3 mRNA expression was higher in

    Nrg1-Het mice compared to WT. In immune challenged animals, JAK1

    mRNA expression was lower in the hippocampus of Nrg1-Het compared

    to WT mice. Conclusion: This study demonstrates that Nrg1 mutation

    alters IL-6 and G-CSF in the periphery and the brain following an immune

    challenge. It further shows alterations in AKT, SOCS3 and JAK1 in the

    brain, key shared signalling pathway molecules. Together these data

    indicate interactions between Nrg1 mutation and immune challenge

    can affect signalling, which may alter neuronal activity in schizophreniarelevant

    brain areas.

Publication Date


  • 2013

Citation


  • Snikeris, P., Huang, X. -F. & Frank, E. (2013). Nrg1 mutation alters cytokine responses relevant to schizophrenia. 33rd Meeting of the Australian Neuroscience Society: Program, Abstracts & List of Registrants (pp. 160-160). Australia: ANS.

Ro Metadata Url


  • http://ro.uow.edu.au/smhpapers/908

Start Page


  • 160

End Page


  • 160

Place Of Publication


  • Australia