In silico gene expression and pathway analysis of DEK in the human brain across the lifespan.

Autor: Greene AN; Neuroscience Graduate Program, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA., Nguyen ET; Department of Psychology, University of Cincinnati, Cincinnati, Ohio, USA., Paranjpe A; Division of Biomedical Informatics, Bioinformatics Collaborative Services, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA., Lane A; Division of Bone Marrow Transplantation and Immune Deficiency, Cancer and Blood Diseases Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA., Privette Vinnedge LM; Division of Oncology, Cancer and Blood Diseases Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA., Solomon MB; Neuroscience Graduate Program, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.; Department of Psychology, University of Cincinnati, Cincinnati, Ohio, USA.
Jazyk: angličtina
Zdroj: The European journal of neuroscience [Eur J Neurosci] 2022 Sep; Vol. 56 (6), pp. 4720-4743. Date of Electronic Publication: 2022 Aug 25.
DOI: 10.1111/ejn.15791
Abstrakt: DEK, a chromatin-remodelling phosphoprotein, is associated with various functions and biological pathways in the periphery, including inflammation, oncogenesis, DNA repair, and transcriptional regulation. We recently identified an association between DEK loss and central nervous system diseases, such as Alzheimer's. To understand DEK's potential role in disease, it is critical to characterize DEK in healthy human brain to distinguish between neural DEK expression and function in healthy versus diseased states like dementia. We utilized two public databases, BrainCloud and Human Brain Transcriptome, and analysed DEK mRNA expression across the lifespan in learning and memory relevant brain regions. Since DEK loss induces phenotypes associated with brain ageing (e.g., DNA damage and apoptosis), we hypothesized that neural DEK expression may be highest during foetal development and lower in elderly individuals. In agreement with this hypothesis, DEK was most prominently expressed during foetal development in all queried forebrain areas, relative to other ages. Consistent with its roles in the periphery, pathways related to DEK in the brain were associated with cellular proliferation, DNA replication and repair, apoptosis, and inflammation. We also found novel neural development-relevant pathways (e.g., synaptic transmission, neurite outgrowth, and myelination) to be enriched from genes correlated with DEK expression. These findings suggest that DEK is important for human brain development. Overall, we highlight age-related changes in neural DEK expression across the human lifespan and illuminate novel biological pathways associated with DEK that are distinct from normal brain ageing. These findings may further our understanding of how DEK impacts brain function and disease susceptibility.
(© 2022 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)
Databáze: MEDLINE
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