Schizophrenia-related endophenotypes in heterozygous neuregulin-1 'knockout' mice
Neuregulin‐1 (NRG1) has been shown to play a role in glutamatergic neurotransmission and is a risk gene for schizophrenia, in which there is evidence for hypoglutamatergic function. Sensitivity to the behavioural effects of the psychotomimetic N‐methyl‐d‐aspartate receptor antagonists MK‐801 and phe...
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| Veröffentlicht in: | The European journal of neuroscience 2010-01, Vol.31 (2), p.349-358 |
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| creator | O'Tuathaigh, C. M. P. Harte, M. O'Leary, C. O'Sullivan, G. J. Blau, C. Lai, D. Harvey, R. P. Tighe, O. Fagan, A. J. Kerskens, C. Reynolds, G. P. Waddington, J. L. |
| description | Neuregulin‐1 (NRG1) has been shown to play a role in glutamatergic neurotransmission and is a risk gene for schizophrenia, in which there is evidence for hypoglutamatergic function. Sensitivity to the behavioural effects of the psychotomimetic N‐methyl‐d‐aspartate receptor antagonists MK‐801 and phencyclidine (PCP) was examined in mutant mice with heterozygous deletion of NRG1. Social behaviour (sociability, social novelty preference and dyadic interaction), together with exploratory activity, was assessed following acute or subchronic administration of MK‐801 (0.1 and 0.2 mg/kg) or PCP (5 mg/kg). In untreated NRG1 mutants, levels of glutamate, N‐acetylaspartate and GABA were determined using high‐performance liquid chromatography and regional brain volumes were assessed using magnetic resonance imaging at 7T. NRG1 mutants, particularly males, displayed decreased responsivity to the locomotor‐activating effects of acute PCP. Subchronic MK‐801 and PCP disrupted sociability and social novelty preference in mutants and wildtypes and reversed the increase in both exploratory activity and social dominance‐related behaviours observed in vehicle‐treated mutants. No phenotypic differences were demonstrated in N‐acetylaspartate, glutamate or GABA levels. The total ventricular and olfactory bulb volume was decreased in mutants. These data indicate a subtle role for NRG1 in modulating several schizophrenia‐relevant processes including the effects of psychotomimetic N‐methyl‐d‐aspartate receptor antagonists. |
| doi_str_mv | 10.1111/j.1460-9568.2009.07069.x |
| format | Article |
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M. P. ; Harte, M. ; O'Leary, C. ; O'Sullivan, G. J. ; Blau, C. ; Lai, D. ; Harvey, R. P. ; Tighe, O. ; Fagan, A. J. ; Kerskens, C. ; Reynolds, G. P. ; Waddington, J. L.</creator><creatorcontrib>O'Tuathaigh, C. M. P. ; Harte, M. ; O'Leary, C. ; O'Sullivan, G. J. ; Blau, C. ; Lai, D. ; Harvey, R. P. ; Tighe, O. ; Fagan, A. J. ; Kerskens, C. ; Reynolds, G. P. ; Waddington, J. L.</creatorcontrib><description>Neuregulin‐1 (NRG1) has been shown to play a role in glutamatergic neurotransmission and is a risk gene for schizophrenia, in which there is evidence for hypoglutamatergic function. Sensitivity to the behavioural effects of the psychotomimetic N‐methyl‐d‐aspartate receptor antagonists MK‐801 and phencyclidine (PCP) was examined in mutant mice with heterozygous deletion of NRG1. Social behaviour (sociability, social novelty preference and dyadic interaction), together with exploratory activity, was assessed following acute or subchronic administration of MK‐801 (0.1 and 0.2 mg/kg) or PCP (5 mg/kg). In untreated NRG1 mutants, levels of glutamate, N‐acetylaspartate and GABA were determined using high‐performance liquid chromatography and regional brain volumes were assessed using magnetic resonance imaging at 7T. NRG1 mutants, particularly males, displayed decreased responsivity to the locomotor‐activating effects of acute PCP. Subchronic MK‐801 and PCP disrupted sociability and social novelty preference in mutants and wildtypes and reversed the increase in both exploratory activity and social dominance‐related behaviours observed in vehicle‐treated mutants. No phenotypic differences were demonstrated in N‐acetylaspartate, glutamate or GABA levels. The total ventricular and olfactory bulb volume was decreased in mutants. These data indicate a subtle role for NRG1 in modulating several schizophrenia‐relevant processes including the effects of psychotomimetic N‐methyl‐d‐aspartate receptor antagonists.</description><identifier>ISSN: 0953-816X</identifier><identifier>EISSN: 1460-9568</identifier><identifier>DOI: 10.1111/j.1460-9568.2009.07069.x</identifier><identifier>PMID: 20074216</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>Animals ; Aspartic Acid - analogs & derivatives ; Aspartic Acid - analysis ; Behavior, Animal - drug effects ; Brain - anatomy & histology ; Brain - metabolism ; Dizocilpine Maleate - pharmacology ; Excitatory Amino Acid Antagonists - pharmacology ; Female ; gamma-Aminobutyric Acid - analysis ; Glutamic Acid - analysis ; imaging ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; mutant model ; Neuregulin-1 - genetics ; Neuregulin-1 - metabolism ; phencyclidine ; Phencyclidine - pharmacology ; Phenotype ; psychosis ; Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors ; Schizophrenia - physiopathology ; Sex Factors ; Social Behavior</subject><ispartof>The European journal of neuroscience, 2010-01, Vol.31 (2), p.349-358</ispartof><rights>The Authors (2010). 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M. P.</creatorcontrib><creatorcontrib>Harte, M.</creatorcontrib><creatorcontrib>O'Leary, C.</creatorcontrib><creatorcontrib>O'Sullivan, G. J.</creatorcontrib><creatorcontrib>Blau, C.</creatorcontrib><creatorcontrib>Lai, D.</creatorcontrib><creatorcontrib>Harvey, R. P.</creatorcontrib><creatorcontrib>Tighe, O.</creatorcontrib><creatorcontrib>Fagan, A. J.</creatorcontrib><creatorcontrib>Kerskens, C.</creatorcontrib><creatorcontrib>Reynolds, G. P.</creatorcontrib><creatorcontrib>Waddington, J. L.</creatorcontrib><title>Schizophrenia-related endophenotypes in heterozygous neuregulin-1 'knockout' mice</title><title>The European journal of neuroscience</title><addtitle>Eur J Neurosci</addtitle><description>Neuregulin‐1 (NRG1) has been shown to play a role in glutamatergic neurotransmission and is a risk gene for schizophrenia, in which there is evidence for hypoglutamatergic function. Sensitivity to the behavioural effects of the psychotomimetic N‐methyl‐d‐aspartate receptor antagonists MK‐801 and phencyclidine (PCP) was examined in mutant mice with heterozygous deletion of NRG1. Social behaviour (sociability, social novelty preference and dyadic interaction), together with exploratory activity, was assessed following acute or subchronic administration of MK‐801 (0.1 and 0.2 mg/kg) or PCP (5 mg/kg). In untreated NRG1 mutants, levels of glutamate, N‐acetylaspartate and GABA were determined using high‐performance liquid chromatography and regional brain volumes were assessed using magnetic resonance imaging at 7T. NRG1 mutants, particularly males, displayed decreased responsivity to the locomotor‐activating effects of acute PCP. Subchronic MK‐801 and PCP disrupted sociability and social novelty preference in mutants and wildtypes and reversed the increase in both exploratory activity and social dominance‐related behaviours observed in vehicle‐treated mutants. No phenotypic differences were demonstrated in N‐acetylaspartate, glutamate or GABA levels. The total ventricular and olfactory bulb volume was decreased in mutants. These data indicate a subtle role for NRG1 in modulating several schizophrenia‐relevant processes including the effects of psychotomimetic N‐methyl‐d‐aspartate receptor antagonists.</description><subject>Animals</subject><subject>Aspartic Acid - analogs & derivatives</subject><subject>Aspartic Acid - analysis</subject><subject>Behavior, Animal - drug effects</subject><subject>Brain - anatomy & histology</subject><subject>Brain - metabolism</subject><subject>Dizocilpine Maleate - pharmacology</subject><subject>Excitatory Amino Acid Antagonists - pharmacology</subject><subject>Female</subject><subject>gamma-Aminobutyric Acid - analysis</subject><subject>Glutamic Acid - analysis</subject><subject>imaging</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>mutant model</subject><subject>Neuregulin-1 - genetics</subject><subject>Neuregulin-1 - metabolism</subject><subject>phencyclidine</subject><subject>Phencyclidine - pharmacology</subject><subject>Phenotype</subject><subject>psychosis</subject><subject>Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors</subject><subject>Schizophrenia - physiopathology</subject><subject>Sex Factors</subject><subject>Social Behavior</subject><issn>0953-816X</issn><issn>1460-9568</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkE1v0zAYgC3ExMrgL6Dcekp4_RE7PnBA1diYpqFpQ0xcrMR5s7pNk2Inot2vx6GjV-aLLft5bOshJKGQ0Tg-rjIqJKQ6l0XGAHQGCqTOdq_I7HjwmsxA5zwtqHw4JW9DWAFAIUX-hpxGRwlG5Yzc3tmle-q3S4-dK1OPbTlgnWBXxz3s-mG_xZC4LlnigL5_2j_2Y0g6HD0-jq3rUprM111v1_04zJONs_iOnDRlG_D983xGvn85v19cptffLr4uPl-nNgehU4uVrZTWFRO24QwLigA5R6YLWtOKQlk0ykprWcOU0KxQFUBN8waZqGkkz8j8cO_W979GDIPZuGCxbcsO4x-NEkIq0AL-T3Kec6o5jWRxIK3vQ_DYmK13m9LvDQUzlTcrMwU2U2AzlTd_y5tdVD88PzJWG6yP4r_UEfh0AH67FvcvvticX91Mq-inB9-FAXdHv_RrIxVXuflxc2GuHtjPxeKOm0v-B7DroX0</recordid><startdate>201001</startdate><enddate>201001</enddate><creator>O'Tuathaigh, C. M. P.</creator><creator>Harte, M.</creator><creator>O'Leary, C.</creator><creator>O'Sullivan, G. J.</creator><creator>Blau, C.</creator><creator>Lai, D.</creator><creator>Harvey, R. P.</creator><creator>Tighe, O.</creator><creator>Fagan, A. J.</creator><creator>Kerskens, C.</creator><creator>Reynolds, G. P.</creator><creator>Waddington, J. L.</creator><general>Blackwell Publishing Ltd</general><scope>BSCLL</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>7TK</scope></search><sort><creationdate>201001</creationdate><title>Schizophrenia-related endophenotypes in heterozygous neuregulin-1 'knockout' mice</title><author>O'Tuathaigh, C. M. P. ; Harte, M. ; O'Leary, C. ; O'Sullivan, G. J. ; Blau, C. ; Lai, D. ; Harvey, R. P. ; Tighe, O. ; Fagan, A. J. ; Kerskens, C. ; Reynolds, G. P. ; Waddington, J. 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L.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Schizophrenia-related endophenotypes in heterozygous neuregulin-1 'knockout' mice</atitle><jtitle>The European journal of neuroscience</jtitle><addtitle>Eur J Neurosci</addtitle><date>2010-01</date><risdate>2010</risdate><volume>31</volume><issue>2</issue><spage>349</spage><epage>358</epage><pages>349-358</pages><issn>0953-816X</issn><eissn>1460-9568</eissn><abstract>Neuregulin‐1 (NRG1) has been shown to play a role in glutamatergic neurotransmission and is a risk gene for schizophrenia, in which there is evidence for hypoglutamatergic function. Sensitivity to the behavioural effects of the psychotomimetic N‐methyl‐d‐aspartate receptor antagonists MK‐801 and phencyclidine (PCP) was examined in mutant mice with heterozygous deletion of NRG1. Social behaviour (sociability, social novelty preference and dyadic interaction), together with exploratory activity, was assessed following acute or subchronic administration of MK‐801 (0.1 and 0.2 mg/kg) or PCP (5 mg/kg). In untreated NRG1 mutants, levels of glutamate, N‐acetylaspartate and GABA were determined using high‐performance liquid chromatography and regional brain volumes were assessed using magnetic resonance imaging at 7T. NRG1 mutants, particularly males, displayed decreased responsivity to the locomotor‐activating effects of acute PCP. Subchronic MK‐801 and PCP disrupted sociability and social novelty preference in mutants and wildtypes and reversed the increase in both exploratory activity and social dominance‐related behaviours observed in vehicle‐treated mutants. No phenotypic differences were demonstrated in N‐acetylaspartate, glutamate or GABA levels. The total ventricular and olfactory bulb volume was decreased in mutants. These data indicate a subtle role for NRG1 in modulating several schizophrenia‐relevant processes including the effects of psychotomimetic N‐methyl‐d‐aspartate receptor antagonists.</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>20074216</pmid><doi>10.1111/j.1460-9568.2009.07069.x</doi><tpages>10</tpages></addata></record> |
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| subjects | Animals Aspartic Acid - analogs & derivatives Aspartic Acid - analysis Behavior, Animal - drug effects Brain - anatomy & histology Brain - metabolism Dizocilpine Maleate - pharmacology Excitatory Amino Acid Antagonists - pharmacology Female gamma-Aminobutyric Acid - analysis Glutamic Acid - analysis imaging Male Mice Mice, Inbred C57BL Mice, Knockout mutant model Neuregulin-1 - genetics Neuregulin-1 - metabolism phencyclidine Phencyclidine - pharmacology Phenotype psychosis Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors Schizophrenia - physiopathology Sex Factors Social Behavior |
| title | Schizophrenia-related endophenotypes in heterozygous neuregulin-1 'knockout' mice |
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