Cortical gene expression in the neonatal ventral-hippocampal lesion rat model

Wong, Albert H.C.; Lipska, Barbara K.; Likhodi, Olga; Boffa, Ernie; Weinberger, Daniel R.; Kennedy, James L.; Van Tol, Hubert H.M.

doi:10.1016/j.schres.2005.03.011

« Previous Next »Schizophrenia Research
Volume 77, Issue 2 , Pages 261-270, 15 September 2005

Cortical gene expression in the neonatal ventral-hippocampal lesion rat model

Albert H.C. Wong
- Department of Psychiatry, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
- Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
- Centre for Addiction and Mental Health, Toronto, Ontario, Canada M5T 1R8
- Department of Pharmacology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
- Corresponding author. Room 711, Centre for Addiction and Mental Health, 250 College Street, Toronto, Ontario, Canada M5T 1R8. Tel.: +1 416 535 8501x4010; fax: +1 416 979 4663.
Barbara K. Lipska
- Clinical Brain Disorders Branch, National Institutes of Mental Health, Bethesda, Maryland, USA
Olga Likhodi
- Centre for Addiction and Mental Health, Toronto, Ontario, Canada M5T 1R8
Ernie Boffa
- Department of Psychiatry, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
- Centre for Addiction and Mental Health, Toronto, Ontario, Canada M5T 1R8
Daniel R. Weinberger
- Clinical Brain Disorders Branch, National Institutes of Mental Health, Bethesda, Maryland, USA
James L. Kennedy
- Department of Psychiatry, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
- Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
- Centre for Addiction and Mental Health, Toronto, Ontario, Canada M5T 1R8
Hubert H.M. Van Tol
- Department of Psychiatry, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
- Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
- Centre for Addiction and Mental Health, Toronto, Ontario, Canada M5T 1R8
- Department of Pharmacology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada

Received 18 January 2005; received in revised form 4 March 2005; accepted 15 March 2005.

Abstract

Schizophrenia is a chronic, debilitating psychotic illness of unknown etiology that has been the subject of many genetic studies. We studied the neonatal ventral-hippocampal lesioned rat as an animal model of schizophrenia in order to identify novel candidate genes for schizophrenia. Temporal and frontal cortices were assessed using cDNA microarrays for differences in mRNA expression associated with the lesion, haloperidol treatment and in two rat strains with differential sensitivity to the behavioural effects of the lesion. Genes that had altered expression levels as a result of the lesion, that were normalized by haloperidol treatment, and that differed between rat strains were selected. The pattern of differential transcription was confirmed with quantitative PCR for all six candidate genes: large conductance calcium-activated potassium channel, subfamily M, beta member 1 (Kcnmb1); doublecortex (dcx); adenylyl cyclase-associated protein 1 (CAP1); adenosine monophosphate deaminase 2-isoform L (AMPD2); malic enzyme 3, NADP(+)-dependent, mitochondrial (Me3); and aspartylglucosaminidase (AGA). None of these genes has been extensively studied in schizophrenia, and further work with post-mortem tissue and genetic studies are ongoing.

Keywords: Schizophrenia, Genomics, Microarray, Ventral-hippocampal lesion, Animal models, Genetics, mRNA