Dataset Information

Intracellular inflammatory and antioxidant pathways in postmortem frontal cortex of subjects with major depression: effect of antidepressants.

ABSTRACT:

Background

Studies show that Toll-like receptors (TLRs), members of the innate immune system, might participate in the pathogenesis of the major depressive disorder (MDD). However, evidence of this participation in the brain of patients with MDD has been elusive.

Methods

This work explores whether the protein expression by immunodetection assays (Western blot) of elements of TLR-4 pathways controlling inflammation and the oxidative/nitrosative stress are altered in postmortem dorsolateral prefrontal cortex of subjects with MDD. The potential modulation induced by the antidepressant treatment on these parameters was also assessed. Thirty MDD subjects (15 antidepressant-free and 15 under antidepressant treatment) were matched for gender and age to 30 controls in a paired design.

Results

No significant changes in TLR-4 expression were detected. An increased expression of the TLR-4 endogenous ligand Hsp70 (+?33%), but not of Hsp60, and the activated forms of mitogen-activated protein kinases (MAPKs) p38 (+?47%) and JNK (+?56%) was observed in MDD. Concomitantly, MDD subjects present a 45% decreased expression of DUSP2 (a regulator of MAPKs) and reduced (-?21%) expression of the antioxidant nuclear factor Nrf2. Antidepressant treatment did not modify the changes detected in the group with MDD and actually increased (+?25%) the expression of p11, a protein linked with the transport of neurotransmitters and depression.

Conclusion

Data indicate an altered TLR-4 immune response in the brain of subjects with MDD. Additional research focused on the mechanisms contributing to the antidepressant-induced TLR-4 pathway modulation is warranted and could help to develop new treatment strategies for MDD.

SUBMITTER: Martin-Hernandez D

PROVIDER: S-EPMC6122627 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Publications

Intracellular inflammatory and antioxidant pathways in postmortem frontal cortex of subjects with major depression: effect of antidepressants.

Martín-Hernández David D Caso Javier R JR Javier Meana J J Callado Luis F LF Madrigal José L M JLM García-Bueno Borja B Leza Juan C JC

Journal of neuroinflammation 20180904 1

<h4>Background</h4>Studies show that Toll-like receptors (TLRs), members of the innate immune system, might participate in the pathogenesis of the major depressive disorder (MDD). However, evidence of this participation in the brain of patients with MDD has been elusive.<h4>Methods</h4>This work explores whether the protein expression by immunodetection assays (Western blot) of elements of TLR-4 pathways controlling inflammation and the oxidative/nitrosative stress are altered in postmortem dors ...[more]

PMID: 30180869

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Project description:ObjectivesRecently, 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.MethodsWe 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.ResultsThere 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.ConclusionsThis 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.

Dataset Information

Intracellular inflammatory and antioxidant pathways in postmortem frontal cortex of subjects with major depression: effect of antidepressants.

Background

Methods

Results

Conclusion

Publications

Intracellular inflammatory and antioxidant pathways in postmortem frontal cortex of subjects with major depression: effect of antidepressants.

Similar Datasets

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