title: Perinatal phencyclidine administration decreases the density of cortical interneurons and increases the expression of neuregulin-1.
abstract: BACKGROUND
  Perinatal phencyclidine (PCP) administration in rat blocks the N-methyl D-aspartate receptor (NMDAR) and causes symptoms reminiscent of schizophrenia in human. A growing body of evidence suggests that alterations in γ-aminobutyric acid (GABA) interneuron neurotransmission may be associated with schizophrenia. Neuregulin-1 (NRG-1) is a trophic factor important for neurodevelopment, synaptic plasticity, and wiring of GABA circuits.
  
  
  OBJECTIVE
  The aim of this study was to determine the long-term effects of perinatal PCP administration on the projection and local circuit neurons and NRG-1 expression in the cortex and hippocampus.
  
  
  METHODS
  Rats were treated on postnatal day 2 (P2), P6, P9, and P12 with either PCP (10 mg/kg) or saline. Morphological studies and determination of NRG-1 expression were performed at P70.
  
  
  RESULTS
  We demonstrate reduced densities of principal neurons in the CA3 and dentate gyrus (DG) subregions of the hippocampus and a reduction of major interneuronal populations in all cortical and hippocampal regions studied in PCP-treated rats compared with controls. For the first time, we show the reduced density of reelin- and somatostatin-positive cells in the cortex and hippocampus of animals perinatally treated with PCP. Furthermore, an increase in the numbers of perisomatic inhibitory terminals around the principal cells was observed in the motor cortex and DG. We also show that perinatal PCP administration leads to an increased NRG-1 expression in the cortex and hippocampus.
  
  
  CONCLUSIONS
  Taken together, our findings demonstrate that perinatal PCP administration increases NRG-1 expression and reduces the number of projecting and local circuit neurons, revealing complex consequences of NMDAR blockade.
authors: Institute of Medical and Clinical Biochemistry, School of Medicine, University of Belgrade, Pasterova 2, 11000 Belgrade, Serbia. nevena.radonjic@med.bg.ac.rs
authors: Nevena V
authors: NV
authors: Radonjić
authors: Igor
authors: I
authors: Jakovcevski
authors: Vladimir
authors: V
authors: Bumbaširević
authors: Nataša D
authors: ND
authors: Petronijević
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002540:Cerebral Cortex / Q000187:drug effects / Q000473:pathology; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000633:toxicity*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology; D007395:Interneurons / Q000187:drug effects / Q000378:metabolism; D008297:Male; D020890:Neuregulin-1 / Q000235:genetics*; D010622:Phencyclidine / Q000008:administration & dosage / Q000633:toxicity*; D011247:Pregnancy; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D000091042:Reelin Protein; D013997:Time Factors
chemical_list: D018691:Excitatory Amino Acid Antagonists; D020890:Neuregulin-1; D016194:Receptors, N-Methyl-D-Aspartate; D000091042:Reelin Protein; C000717129:Reln protein, rat; C000717127:RELN protein, human; D010622:Phencyclidine
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