Examination of schizophrenia endophenotypes in the heterozygous neuregulin-1 ko mouse: a psychopharmacological and magnetic resonance imaging study

• Autorzy: O'Tuathaigh C. , O'Sullivan G. , Tighe O. , O'Leary C. , Desbonnet L. , Lai D. , Harvey R. , Croke D. , Waddington J.
• Języki publikacji: EN

Abstrakty

EN

Meta-analysis has confi rmed the association between the neuregulin-1 (NRG1) gene risk to develop schizophrenia. Neuregulin-1, alongside several other risk genes, is known to play a role in glutamatergic neurotransmission. There is a substantive body of evidence for hypoglutamatergic function in schizophrenia; the psychotomimetic activity of non-competitive NMDA antagonists MK-801 and phencyclidine (PCP) is complemented by NMDA defi cits in post-mortem brain in schizophrenia. In the present study, differential sensitivity to the behavioural effects of MK-801 and PCP was examined in mice containing partial deletion of the NRG1 gene in order to elucidate the relationship between NRG1 genotype and the psychotomimetic effects of NMDA receptor antagonism. Changes in social behaviour and exploratory activity were assessed in NRG1 mutants vs. wildtypes following acute or subchronic administration of MK-801 or PCP. Neuregulin-1 mutants and wildtype controls mice were also examined by magnetic resonance (MR) volumetry using high-resolution T2-weighted imaging at 7 T in order to examine effects of NRG1 genotype on presence of schizophrenia-relevant structural brain endophenotypes. The results indicate that NRG1 knockout mice display (a) altered responsivity to NMDA receptor antagonists compared to controls (b) volumetric changes in brain areas implicated in schizophrenia. This work was funded by Science Foundation Ireland & Health Research Board of Ireland.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2009
• Tom: 69
• Numer: 3
• Opis fizyczny: p.348

Twórcy

autor

O'Tuathaigh C.

• Department of Molecular and Cellular Therapeutic, Royal College of Surgeons in Ireland, Dublin, Ireland

autor

O'Sullivan G.

• Department of Molecular and Cellular Therapeutic, Royal College of Surgeons in Ireland, Dublin, Ireland

autor

Tighe O.

• Department of Molecular and Cellular Therapeutic, Royal College of Surgeons in Ireland, Dublin, Ireland

autor

O'Leary C.

• Department of Molecular and Cellular Therapeutic, Royal College of Surgeons in Ireland, Dublin, Ireland

autor

Desbonnet L.

• Department of Molecular and Cellular Therapeutic, Royal College of Surgeons in Ireland, Dublin, Ireland

autor

Lai D.

• Department of Developmental Biology, Victor Chang Cardiac Research Institute, Sydney, Australia

autor

Harvey R.

• Department of Developmental Biology, Victor Chang Cardiac Research Institute, Sydney, Australia

autor

Croke D.

• Department of Molecular and Cellular Therapeutic, Royal College of Surgeons in Ireland, Dublin, Ireland

autor

Waddington J.

• Department of Molecular and Cellular Therapeutic, Royal College of Surgeons in Ireland, Dublin, Ireland