Perinatal phencyclidine administration decreases the density of cortical interneurons and increases the expression of neuregulin-1

TY - JOUR

T1 - Perinatal phencyclidine administration decreases the density of cortical interneurons and increases the expression of neuregulin-1

AU - Radonjić, Nevena V

AU - Jakovcevski, Igor

AU - Bumbaširević, Vladimir

AU - Petronijević, Nataša D

PY - 2013/6/1

Y1 - 2013/6/1

N2 - RATIONALE: 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.OBJECTIVES: 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.CONCLUSION: 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.

AB - RATIONALE: 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.OBJECTIVES: 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.CONCLUSION: 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.

KW - Animals

KW - Animals, Newborn

KW - Cerebral Cortex

KW - Excitatory Amino Acid Antagonists

KW - Female

KW - Gene Expression Regulation

KW - Hippocampus

KW - Interneurons

KW - Male

KW - Neuregulin-1

KW - Phencyclidine

KW - Pregnancy

KW - Rats

KW - Receptors, N-Methyl-D-Aspartate

KW - Time Factors

U2 - 10.1007/s00213-013-2999-7

DO - 10.1007/s00213-013-2999-7

M3 - SCORING: Journal article

C2 - 23380917

VL - 227

SP - 673

EP - 683

JO - PSYCHOPHARMACOLOGY

JF - PSYCHOPHARMACOLOGY

SN - 0033-3158

IS - 4

ER -