Dataset Information

KEOPS complex expression in the frontal cortex in major depression and schizophrenia.

ABSTRACT:

Objectives

Recently, the presence of a complete five subunit Kinase, Endopeptidase and Other Proteins of small Size (KEOPS) complex was confirmed in humans. The highly conserved KEOPS protein complex has established roles in tRNA modification, protein translation and telomere homeostasis in yeast, but little is known about KEOPS mRNA expression and function in human brain and disease. Here, we characterise KEOPS expression in post-mortem tissue from subjects diagnosed with major depression (MDD) and schizophrenia and assess whether KEOPS is associated with telomere length dysregulation in neuropsychiatric disorders.

Methods

We assessed mRNA expression of KEOPS complex subunits TP53RK, TPRKB, GON7, LAGE3, OSGEP, and OSGEP mitochondrial ortholog OSGEPL1 in the dorsolateral prefrontal cortex (DLPFC) of subjects with MDD, schizophrenia and matched non-psychiatrically ill controls (n = 20 per group) using qPCR. We conducted bioinformatic analysis using Kaleidoscope, data mining post-mortem transcriptomic datasets to characterise KEOPS expression in human brain. Finally, we assayed relative telomere length in the DLPFC using a qPCR-based assay and carried out correlation analysis with KEOPS subunit mRNA expression to determine if the KEOPS complex is associated with telomere length dysregulation in neuropsychiatric disorders.

Results

There were no significant changes in KEOPS mRNA expression in the DLPFC in MDD or schizophrenia compared to non-psychiatrically ill controls. Relative telomere length was not significantly altered in MDD or schizophrenia, nor was there an association between relative telomere length and KEOPS subunit gene expression in these subjects.

Conclusions

This study is the first to describe KEOPS complex expression in post-mortem brain and neuropsychiatric disorders. KEOPS subunit mRNA expression is not significantly altered in the DLPFC in MDD or schizophrenia. Unlike in yeast, the KEOPS complex does not appear to play a role in telomere length regulation in humans or in neuropsychiatric disorders.

SUBMITTER: Abel ME

PROVIDER: S-EPMC8005497 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature

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Publications

KEOPS complex expression in the frontal cortex in major depression and schizophrenia.

Abel Mackenzie E ME Zhang Xiaolu X Asah Sophie M SM Wolfinger Alyssa A McCullumsmith Robert E RE O'Donovan Sinead M SM

The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry 20200929 6

<h4>Objectives</h4>Recently, the presence of a complete five subunit Kinase, Endopeptidase and Other Proteins of small Size (KEOPS) complex was confirmed in humans. The highly conserved KEOPS protein complex has established roles in tRNA modification, protein translation and telomere homeostasis in yeast, but little is known about KEOPS mRNA expression and function in human brain and disease. Here, we characterise KEOPS expression in post-mortem tissue from subjects diagnosed with major depressi ...[more]

PMID: 32914678

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Project description:BackgroundRetinoids regulate gene expression in different cells and tissues at the transcriptional level. Retinoic acid transcriptionally regulates downstream regulatory molecules, including enzymes, transcription factors, cytokines, and cytokine receptors. Animal models indicate an involvement of retinoid signaling pathways in the regulation of synaptic plasticity and learning, especially in the hippocampus. Retinoic acid-inducible or induced gene 1 (RAI-1) is induced during neuronal differentiation, and was associated with the severity of the phenotype and response to medication in schizophrenic patients.MethodsIn the present study, we used immunohistochemistry to investigate the expression of RAI-1 in 60 brains from the Stanley Neuropathology Consortium (15 cases each from controls and from patients with schizophrenia, bipolar disorder, and major depression). Rating scores for density and intensity were determined in the dorsolateral prefrontal cortex.ResultsAll four groups showed high interindividual variation. RAI-1-positive cells were identified as neurons and astrocytes. Significantly increased intensities in cortical neurons were noted in all three major psychiatric groups compared with controls. The density of RAI-1-positive neurons was increased (P=0.06) in schizophrenia and bipolar disorder. In bipolar disorder, RAI-1-positive astrocytes in gray matter showed a significantly increased intensity and compound value. Thus, a significant increase in the parameters measured was found in schizophrenia, bipolar disorder, and major depression.ConclusionOur study shows a significant increase in expression of RAI-1 in the brains from patients with schizophrenia, bipolar disorder, or major depression. The increased expression might reflect altered signaling pathways, like that for retinoic acid. The underlying mechanisms leading to the increased expression and its functional consequences are so far unknown, and remain to be investigated in future studies.

Dataset Information

KEOPS complex expression in the frontal cortex in major depression and schizophrenia.

Objectives

Methods

Results

Conclusions

Publications

KEOPS complex expression in the frontal cortex in major depression and schizophrenia.

Similar Datasets

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