title: Mitochondrial complex I subunits are altered in rats with neonatal ventral hippocampal damage but not in rats exposed to oxygen restriction at neonatal age.
abstract: Several independent lines of evidence suggest mitochondrial dysfunction in schizophrenia in brain and periphery, including mitochondrial hypoplasia, dysfunction of the oxidative phosphorylation system, and altered mitochondrial-related gene expression. In an attempt to decipher whether mitochondrial complex I abnormality in schizophrenia is a core pathophysiological process or is attributable to medication, we studied two animal models of schizophrenia related to the neurodevelopmental hypothesis of this disorder. Protein levels of complex I subunits, 24, 51, and 75 kDa, were assessed in neonatal ventral hippocampal lesion rat model and in rats exposed to hypoxia at a neonatal age. In the prefrontal cortex, a major anatomical substrate of schizophrenia, neonatal ventral hippocampal lesion induced a significant prepubertal increase and postpubertal decrease in all three subunits of complex I as compared to sham-treated rats, while no change was observed in the cingulate cortex. Neonatal exposure to hypoxia did not affect protein levels of any of the three subunits in the prefrontal cortex. An age-dependent increase in the expression of complex I subunits was observed, which was distorted in the prefrontal cortex by the neonatal ventral hippocampal lesion. Complex I alterations in schizophrenia-related neurodevelopmental rat models appear to be brain region and animal model dependent. The results of this study support previous findings suggesting abnormal complex I expression as a pathological characteristic of schizophrenia rather than an effect of medication.
authors.affiliation: Laboratory of Psychobiology, Department of Psychiatry, Rambam Medical Center and B. Rappaport Faculty of Medicine, Technion ITT, P.O. Box 9649, Haifa, 31096, Israel. shachar@tx.technion.ac.il
authors.forename: Dorit
authors.initials: D
authors.lastname: Ben-Shachar
authors.forename: Carmit
authors.initials: C
authors.lastname: Nadri
authors.forename: Rachel
authors.initials: R
authors.lastname: Karry
authors.forename: Galila
authors.initials: G
authors.lastname: Agam
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000033:anatomy & histology / Q000378:metabolism; D042967:Electron Transport Complex I / Q000502:physiology*; D005260:Female; D006624:Hippocampus / Q000473:pathology*; D006801:Humans; D000860:Hypoxia; D008928:Mitochondria / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism; D011247:Pregnancy; D021122:Protein Subunits / Q000378:metabolism; D011627:Puberty; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D021122:Protein Subunits; D042967:Electron Transport Complex I; D010100:Oxygen
references.citation: J Biol Chem. 1998 May 22;273(21):12753-7
references.pmid: 9582300
references.citation: Am J Psychiatry. 2002 Jul;159(7):1080-92
references.pmid: 12091183
references.citation: Neuroscience. 2001;105(1):7-17
references.pmid: 11483296
references.citation: Biol Psychiatry. 2005 Jul 15;58(2):85-96
references.pmid: 16038679
references.citation: Ann Neurol. 1993 May;33(5):512-7
references.pmid: 8098932
references.citation: Schizophr Bull. 2006 Jan;32(1):3-8
references.pmid: 16306181
references.citation: Genomics. 1995 Sep 1;29(1):217-24
references.pmid: 8530074
references.citation: Mol Psychiatry. 2002;7(9):995-1001
references.pmid: 12399953
references.citation: Sleep Breath. 2002 Dec;6(4):205-10
references.pmid: 12524574
references.citation: Neurosci Biobehav Rev. 2003 Jan-Mar;27(1-2):91-101
references.pmid: 12732226
references.citation: Schizophr Res. 2007 Aug;94(1-3):354-8
references.pmid: 17566709
references.citation: Prog Neurobiol. 2004 Aug;73(6):397-445
references.pmid: 15313334
references.citation: Philos Trans R Soc Lond B Biol Sci. 1999 Feb 28;354(1381):365-72
references.pmid: 10212485