Cortical gene expression in the neonatal ventral-hippocampal lesion rat model.
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.
Wong
Albert H C
AH
Department of Psychiatry, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada. albert.wong@utoronto.ca
Lipska
Barbara K
BK
Likhodi
Olga
O
Boffa
Ernie
E
Weinberger
Daniel R
DR
Kennedy
James L
JL
Van Tol
Hubert H M
HH
D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D004195:Disease Models, Animal; D000089662:Doublecortin Protein; D005625:Frontal Lobe / Q000187:drug effects / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D006220:Haloperidol / Q000494:pharmacology; D006624:Hippocampus / Q000473:pathology; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D012559:Schizophrenia / Q000235:genetics* / Q000378:metabolism; D013702:Temporal Lobe / Q000187:drug effects / Q000378:metabolism*
C000714848:Dcx protein, rat; D000089662:Doublecortin Protein; D012333:RNA, Messenger; D006220:Haloperidol