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

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.