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Perinatal administration of phencyclidine alters expression of Lingo-1 signaling pathway proteins in the prefrontal cortex of juvenile and adult rats

Journal Article


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Abstract


  • Postnatal administration of phencyclidine (PCP)

    in rodents causes major brain dysfunction

    leading to severe disturbances in behavior

    lasting into adulthood. This model is routinely

    employed to model psychiatric

    disorders such as schizophrenia, as it reflects schizophrenia

    related brain disturbances in

    cluding increased apoptosis, a

    nd disruptions to myelin and

    plasticity processes. Leucine

    -rich repeat and immunoglobulin

    domain-containing protein,

    Lingo-1, is a potent negative regulator of both

    axonal myelination and neurite extension. The

    Nogo receptor (NgR)/TNF receptor orphan Y (T

    ROY) and/or p75 complex, With No Lysine

    (K) (WNK1) and Myelin transcription factor-1 (Myt1) are co-receptors or co-factors in Lingo-

    1 signaling pathways in the brain. We have examined the developmental trajectory of these

    proteins in a neurodevelopmenta

    l model of schizophren

    ia using PCP to determine if Lingo-1

    pathways are altered in the prefrontal cortex

    throughout different stages of life. Sprague

    Dawley rats were injected with PCP (10mg/kg) or saline on postnatal days (PN)7, 9 and 11 and

    sacrificed at PN12, 5 weeks or 14 weeks for meas

    urement of Lingo-1 signaling proteins in the

    prefrontal cortex. Myt1 was decreased by

    PCP at PN12 (p=0.045), and at 14 weeks PCP

    increased Lingo-1 (p=0.037), TROY (p=0.017) an

    d WNK1 (p=0.003) expression. This is the

    first study reporting an alteration in Lingo-1 sign

    aling proteins in the ra

    t prefrontal cortex both

    directly after PCP treatment in early development and in adulthood. We propose that Lingo-1

    pathways may be negatively regulating myelination and neurite outgrowth following the

    administration of PCP, and that this may have implications for the cortical dysfunction

    observed in schizophrenia.

Publication Date


  • 2018

Citation


  • Andrews, J. L., Newell, K. A., Matosin, N., Huang, X. & Fernandez, F. (2018). Perinatal administration of phencyclidine alters expression of Lingo-1 signaling pathway proteins in the prefrontal cortex of juvenile and adult rats. Neuronal Signaling, Online First

Ro Full-text Url


  • http://ro.uow.edu.au/cgi/viewcontent.cgi?article=2284&context=ihmri

Ro Metadata Url


  • http://ro.uow.edu.au/ihmri/1257

Volume


  • Online First

Place Of Publication


  • London

Abstract


  • Postnatal administration of phencyclidine (PCP)

    in rodents causes major brain dysfunction

    leading to severe disturbances in behavior

    lasting into adulthood. This model is routinely

    employed to model psychiatric

    disorders such as schizophrenia, as it reflects schizophrenia

    related brain disturbances in

    cluding increased apoptosis, a

    nd disruptions to myelin and

    plasticity processes. Leucine

    -rich repeat and immunoglobulin

    domain-containing protein,

    Lingo-1, is a potent negative regulator of both

    axonal myelination and neurite extension. The

    Nogo receptor (NgR)/TNF receptor orphan Y (T

    ROY) and/or p75 complex, With No Lysine

    (K) (WNK1) and Myelin transcription factor-1 (Myt1) are co-receptors or co-factors in Lingo-

    1 signaling pathways in the brain. We have examined the developmental trajectory of these

    proteins in a neurodevelopmenta

    l model of schizophren

    ia using PCP to determine if Lingo-1

    pathways are altered in the prefrontal cortex

    throughout different stages of life. Sprague

    Dawley rats were injected with PCP (10mg/kg) or saline on postnatal days (PN)7, 9 and 11 and

    sacrificed at PN12, 5 weeks or 14 weeks for meas

    urement of Lingo-1 signaling proteins in the

    prefrontal cortex. Myt1 was decreased by

    PCP at PN12 (p=0.045), and at 14 weeks PCP

    increased Lingo-1 (p=0.037), TROY (p=0.017) an

    d WNK1 (p=0.003) expression. This is the

    first study reporting an alteration in Lingo-1 sign

    aling proteins in the ra

    t prefrontal cortex both

    directly after PCP treatment in early development and in adulthood. We propose that Lingo-1

    pathways may be negatively regulating myelination and neurite outgrowth following the

    administration of PCP, and that this may have implications for the cortical dysfunction

    observed in schizophrenia.

Publication Date


  • 2018

Citation


  • Andrews, J. L., Newell, K. A., Matosin, N., Huang, X. & Fernandez, F. (2018). Perinatal administration of phencyclidine alters expression of Lingo-1 signaling pathway proteins in the prefrontal cortex of juvenile and adult rats. Neuronal Signaling, Online First

Ro Full-text Url


  • http://ro.uow.edu.au/cgi/viewcontent.cgi?article=2284&context=ihmri

Ro Metadata Url


  • http://ro.uow.edu.au/ihmri/1257

Volume


  • Online First

Place Of Publication


  • London