Deficient hippocampal neuron expression of proteasome, ubiquitin, and mitochondrial genes in multiple schizophrenia cohorts
Autor: | Peng Liu, Michael B. Knable, Vinod Charles, Maree J. Webster, Hiroko Yokoe, C. Anthony Altar, Andrew L. Lemire, Yury V. Bukhman, Linda W. Jurata, Jeffrey Bullard, Jeffrey A. Brockman, Theresa A. Young |
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Rok vydání: | 2004 |
Předmět: |
Psychosis
medicine.medical_specialty Proteasome Endopeptidase Complex Bipolar Disorder Neurite Mitochondrion Hippocampal formation DNA Mitochondrial Severity of Illness Index Internal medicine Gene expression medicine Cytochrome c oxidase Humans Biological Psychiatry Oligonucleotide Array Sequence Analysis Neurons Analysis of Variance Depressive Disorder Major biology Ubiquitin Dentate gyrus Gene Expression Profiling Hydrogen-Ion Concentration medicine.disease medicine.anatomical_structure Endocrinology Electron Transport Chain Complex Proteins Case-Control Studies Dentate Gyrus biology.protein Schizophrenia Neuron Energy Metabolism Neuroscience |
Zdroj: | Biological psychiatry. 58(2) |
ISSN: | 0006-3223 |
Popis: | Background Hippocampal dentate granule neurons are altered in schizophrenia, but it is unknown if their gene expressions change in schizophrenia or other psychiatric diseases. Methods Laser-captured dentate granule neurons from two groups of schizophrenia and control cases and from major depression and bipolar disease cases were examined for alterations in gene expression using complementary DNA (cDNA) microarrays and reverse transcription polymerase chain reaction (RT-PCR). Results Compared with 24 control cases, the 22 schizophrenia patients in both groups revealed decreases in clusters of genes that encode for protein turnover (proteasome subunits and ubiquitin), mitochondrial oxidative energy metabolism (isocitrate, lactate, malate, nicotinamide adenine dinucleotide [NADH], and succinate dehydrogenases; cytochrome C oxidase; adenosine triphosphate [ATP] synthase), and genes associated with neurite outgrowth, cytoskeletal proteins, and synapse plasticity. These changes were not obtained in 9 bipolar cases or 10 major depression cases and were not associated with age, sex, brain weight, body weight, postmortem interval, or drug history. Brain pH contributed to the variance of some genes but was mostly independent of the disease effect. Conclusions Decreases in hippocampal neuron gene expression are consistent with brain imaging and microarray studies of the frontal cortex in schizophrenia. A mitochondrial and ubiquitin-proteasome hypofunctioning of dentate granule neurons may contribute to the deficits of schizophrenia. |
Databáze: | OpenAIRE |
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