Mitochondrial complex I subunits are altered in rats with neonatal ventral hippocampal damage but not in rats exposed to oxygen restriction at neonatal age.
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.
Ben-Shachar
Dorit
D
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
Nadri
Carmit
C
Karry
Rachel
R
Agam
Galila
G
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
D021122:Protein Subunits; D042967:Electron Transport Complex I; D010100:Oxygen
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