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

Jessica L Andrews; Kelly A Newell; Natalie Matosin; Xu-Feng Huang; Francesca Fernandez

doi:10.1042/NS20180059

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

Neuronal Signal. 2018 Sep 28;2(3):NS20180059. doi: 10.1042/NS20180059. eCollection 2018 Sep.

Authors

Jessica L Andrews^{1

2

3}, Kelly A Newell^{1

2

3}, Natalie Matosin^{1

2

3

4

5}, Xu-Feng Huang^{1

2

3}, Francesca Fernandez^{1

2

3

6

7}

Affiliations

¹ Centre for Medical and Molecular Bioscience, Faculty of Science, Medicine and Health, University of Wollongong, Wollongong, NSW, Australia.
² Illawarra Health and Medical Research Institute, University of Wollongong, Wollongong, NSW, Australia.
³ Schizophrenia Research Institute, Sydney, NSW, Australia.
⁴ School of Psychiatry, Faculty of Medicine, University of New South Wales, Sydney, Australia.
⁵ Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Munich, Germany.
⁶ Faculty of Social Sciences, University of Wollongong, Wollongong, NSW, Australia.
⁷ School of Science, Faculty of Health Sciences, Australian Catholic University, Brisbane, Australia.

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 including increased apoptosis, and disruptions to myelin and plasticity processes. Leucine-rich repeat and Immunoglobin-like domain-containing protein 1 (Lingo-1) is a potent negative regulator of both axonal myelination and neurite extension. The Nogo receptor (NgR)/tumor necrosis factor (TNF) receptor orphan Y (TROY) and/or p75 neurotrophin receptor (p75) complex, with no lysine (K) (WNK1) and myelin transcription factor 1 (Myt1) are co-receptors or cofactors in Lingo-1 signaling pathways in the brain. We have examined the developmental trajectory of these proteins in a neurodevelopmental model of schizophrenia 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 (10 mg/kg) or saline on postnatal days (PN)7, 9, and 11 and killed at PN12, 5 or 14 weeks for measurement 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), and WNK1 (P=0.003) expression. This is the first study reporting an alteration in Lingo-1 signaling proteins in the rat 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.

Keywords: Lingo-1 signaling; neurodevelopment; phencyclidine animal model; prefrontal cortex; schizophrenia.