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Perinatal phencyclidine treatment alters neuregulin 1/erbB4 expression and activation in later life

Journal Article


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Abstract


  • Schizophrenia is a complex and devastating mental disorder of unknown etiology. Hypofunction

    of N-methyl-D-aspartate (NMDA) receptors are implicated in the disorder, since phencyclidine

    (PCP) and other NMDA receptor antagonists mimic schizophrenia-like symptoms in humans and

    animals so well. Moreover, genetic linkage and post mortem studies strongly suggest a role for

    altered neuregulin 1 (Nrg1)/erbB4 signaling in schizophrenia pathology. This study investigated

    the relationship between the NMDA receptor and Nrg1 signaling pathways using the perinatal

    PCP animal model. Rats (n=5/group) were treated with PCP (10 mg/kg) or saline on postnatal

    days (PN) 7, 9 and 11 and were sacrificed on PN12, 5 weeks and 20 weeks for biochemical analyses.

    Western blotting was used to determine total and phosphorylated levels of proteins involved in

    NMDA receptor/Nrg1 signaling in the prefrontal cortex and hippocampus. In the cortex, PCP treatment

    altered Nrg1/erbB4 expression levels throughout development, including decreased Nrg1 and

    erbB4 at PN12 (−25–30%; pb0.05); increased erbB4 and p-erbB4 (+18–27%; pb0.01) at 5 weeks;

    and decreased erbB4 and p-erbB4 (−16–18%; pb0.05) along with increased Nrg1 (+33%; pb0.01)

    at 20 weeks. In the hippocampus, levels of Nrg1/erbB4 were largely unaffected apart from a

    significant decrease in p-erbB4 at 20 weeks (−13%; pb0.001); however NMDA receptor subunits

    and PSD-95 showed increases at PN12 and 5 weeks (+20–32%; pb0.05), and decreases at

    20 weeks (−22–29%; pb0.05). This study shows that NMDA receptor antagonism early in development

    can have long term effects on Nrg1/erbB4 expression which could be important in

    understanding pathological processes which might be involved in schizophrenia.

    © 2011 Elsevier B.V. and ECNP. All rights reserved.

Publication Date


  • 2012

Citation


  • du Bois, T. Marie., Newell, K. Anne. & Huang, X. (2012). Perinatal phencyclidine treatment alters neuregulin 1/erbB4 expression and activation in later life. European Neuropsychopharmacology, 22 (5), 356-363.

Scopus Eid


  • 2-s2.0-84859212663

Ro Full-text Url


  • http://ro.uow.edu.au/cgi/viewcontent.cgi?article=3825&context=hbspapers

Ro Metadata Url


  • http://ro.uow.edu.au/hbspapers/2776

Has Global Citation Frequency


Number Of Pages


  • 7

Start Page


  • 356

End Page


  • 363

Volume


  • 22

Issue


  • 5

Place Of Publication


  • Netherlands

Abstract


  • Schizophrenia is a complex and devastating mental disorder of unknown etiology. Hypofunction

    of N-methyl-D-aspartate (NMDA) receptors are implicated in the disorder, since phencyclidine

    (PCP) and other NMDA receptor antagonists mimic schizophrenia-like symptoms in humans and

    animals so well. Moreover, genetic linkage and post mortem studies strongly suggest a role for

    altered neuregulin 1 (Nrg1)/erbB4 signaling in schizophrenia pathology. This study investigated

    the relationship between the NMDA receptor and Nrg1 signaling pathways using the perinatal

    PCP animal model. Rats (n=5/group) were treated with PCP (10 mg/kg) or saline on postnatal

    days (PN) 7, 9 and 11 and were sacrificed on PN12, 5 weeks and 20 weeks for biochemical analyses.

    Western blotting was used to determine total and phosphorylated levels of proteins involved in

    NMDA receptor/Nrg1 signaling in the prefrontal cortex and hippocampus. In the cortex, PCP treatment

    altered Nrg1/erbB4 expression levels throughout development, including decreased Nrg1 and

    erbB4 at PN12 (−25–30%; pb0.05); increased erbB4 and p-erbB4 (+18–27%; pb0.01) at 5 weeks;

    and decreased erbB4 and p-erbB4 (−16–18%; pb0.05) along with increased Nrg1 (+33%; pb0.01)

    at 20 weeks. In the hippocampus, levels of Nrg1/erbB4 were largely unaffected apart from a

    significant decrease in p-erbB4 at 20 weeks (−13%; pb0.001); however NMDA receptor subunits

    and PSD-95 showed increases at PN12 and 5 weeks (+20–32%; pb0.05), and decreases at

    20 weeks (−22–29%; pb0.05). This study shows that NMDA receptor antagonism early in development

    can have long term effects on Nrg1/erbB4 expression which could be important in

    understanding pathological processes which might be involved in schizophrenia.

    © 2011 Elsevier B.V. and ECNP. All rights reserved.

Publication Date


  • 2012

Citation


  • du Bois, T. Marie., Newell, K. Anne. & Huang, X. (2012). Perinatal phencyclidine treatment alters neuregulin 1/erbB4 expression and activation in later life. European Neuropsychopharmacology, 22 (5), 356-363.

Scopus Eid


  • 2-s2.0-84859212663

Ro Full-text Url


  • http://ro.uow.edu.au/cgi/viewcontent.cgi?article=3825&context=hbspapers

Ro Metadata Url


  • http://ro.uow.edu.au/hbspapers/2776

Has Global Citation Frequency


Number Of Pages


  • 7

Start Page


  • 356

End Page


  • 363

Volume


  • 22

Issue


  • 5

Place Of Publication


  • Netherlands