TY - JOUR
T1 - Cortical gene expression in the neonatal ventral-hippocampal lesion rat model
AU - Wong, Albert H.C.
AU - Lipska, Barbara K.
AU - Likhodi, Olga
AU - Boffa, Ernie
AU - Weinberger, Daniel R.
AU - Kennedy, James L.
AU - Van Tol, Hubert H.M.
N1 - Funding Information:
We would like to acknowledge the support of the Canadian Institutes for Health Research, the Ontario Mental Health Foundation, and the National Institutes for Mental Health. HHMVT holds a Canada Research Chair in Neurobiology, and AHCW is a CIHR Clinician-Scientist Fellow.
PY - 2005/9/15
Y1 - 2005/9/15
N2 - 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.
AB - 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.
KW - Animal models
KW - Genetics
KW - Genomics
KW - Microarray
KW - Schizophrenia
KW - Ventral-hippocampal lesion
KW - mRNA
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U2 - 10.1016/j.schres.2005.03.011
DO - 10.1016/j.schres.2005.03.011
M3 - Article
C2 - 15890497
AN - SCOPUS:23444441478
VL - 77
SP - 261
EP - 270
JO - Schizophrenia Research
JF - Schizophrenia Research
SN - 0920-9964
IS - 2-3
ER -