Perinatal phencyclidine administration decreases the density of cortical interneurons and increases the expression of neuregulin-1
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Perinatal phencyclidine administration decreases the density of cortical interneurons and increases the expression of neuregulin-1. / Radonjić, Nevena V; Jakovcevski, Igor; Bumbaširević, Vladimir; Petronijević, Nataša D.
In: PSYCHOPHARMACOLOGY, Vol. 227, No. 4, 01.06.2013, p. 673-83.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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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 -