1. Perinatal phencyclidine treatment alters neuregulin 1/erbB4 expression and activation in later life
- Author
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du Bois, Teresa Marie, Newell, Kelly Anne, and Huang, Xu-Feng
- Subjects
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PERINATAL pharmacology , *PHENCYCLIDINE , *NEUREGULINS , *OLD age , *SCHIZOPHRENIA , *MENTAL illness , *ETIOLOGY of diseases - Abstract
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 (10mg/kg) or saline on postnatal days (PN) 7, 9 and 11 and were sacrificed on PN12, 5weeks and 20weeks 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%; p <0.05); increased erbB4 and p-erbB4 (+18–27%; p <0.01) at 5weeks; and decreased erbB4 and p-erbB4 (−16–18%; p <0.05) along with increased Nrg1 (+33%; p <0.01) at 20weeks. In the hippocampus, levels of Nrg1/erbB4 were largely unaffected apart from a significant decrease in p-erbB4 at 20weeks (−13%; p <0.001); however NMDA receptor subunits and PSD-95 showed increases at PN12 and 5weeks (+20–32%; p <0.05), and decreases at 20weeks (−22–29%; p <0.05). 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. [Copyright &y& Elsevier]
- Published
- 2012
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