TY - JOUR
T1 - Mitochondrial complex I subunits are altered in rats with neonatal ventral hippocampal damage but not in rats exposed to oxygen restriction at neonatal age
AU - Ben-Shachar, Dorit
AU - Nadri, Carmit
AU - Karry, Rachel
AU - Agam, Galila
N1 - Funding Information:
Role of funding source Funding for this study was provided by the Stanley Medical Research Institute grant. The SMRI had no further role in the study design, in the collection, analysis, and interpretation of data, in the writing of the report; and in the decision to submit the paper for publication.
PY - 2009/6/1
Y1 - 2009/6/1
N2 - 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 agedependent 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.
AB - 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 agedependent 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.
KW - Mitochondrial complex I
KW - Neonatal hypoxia
KW - Neonatal ventral hippocampal lesion
KW - Rat model
KW - Schizophrenia
UR - http://www.scopus.com/inward/record.url?scp=69249231188&partnerID=8YFLogxK
U2 - 10.1007/s12031-008-9144-9
DO - 10.1007/s12031-008-9144-9
M3 - Article
C2 - 18779937
AN - SCOPUS:69249231188
SN - 0895-8696
VL - 38
SP - 143
EP - 151
JO - Journal of Molecular Neuroscience
JF - Journal of Molecular Neuroscience
IS - 2
ER -