Schizophrenia-related endophenotypes in heterozygous neuregulin-1 ‘knockout’ mice

Autor:	Orna Tighe, Colm M. P. O’Tuathaigh, Donna Lai, Richard P. Harvey, Christoph W. Blau, Andrew J. Fagan, Gavin P. Reynolds, Gerard J. O'Sullivan, John L. Waddington, Michael K. Harte, Christian Kerskens, C. O'Leary
Rok vydání:	2010
Předmět:	Male medicine.medical_specialty Psychosis Neuregulin-1 Glutamic Acid Phencyclidine Receptors N-Methyl-D-Aspartate Mice Glutamatergic Sex Factors Internal medicine mental disorders medicine Animals Neuregulin 1 Social Behavior gamma-Aminobutyric Acid Mice Knockout Aspartic Acid Behavior Animal biology General Neuroscience Glutamate receptor Brain Psychotomimetic medicine.disease Mice Inbred C57BL Phenotype Endocrinology Knockout mouse Dyadic interaction Schizophrenia biology.protein Female Dizocilpine Maleate Psychology Excitatory Amino Acid Antagonists Neuroscience medicine.drug
Zdroj:	European Journal of Neuroscience. 31:349-358
ISSN:	1460-9568 0953-816X
DOI:	10.1111/j.1460-9568.2009.07069.x
Popis:	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.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::798ef19d93b7832600501726966b1a16 https://doi.org/10.1111/j.1460-9568.2009.07069.x Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
Nepřihlášeným uživatelům se plný text nezobrazuje	K zobrazení výsledku je třeba se přihlásit.