Proteomic evidence of depression-associated astrocytic dysfunction in the human male olfactory bulb.

Autor: Rahimian R; McGill Group for Suicide Studies, Douglas Mental Health University Institute, Verdun, QC, Canada; Department of Psychiatry, McGill University, Montreal, QC, Canada., Perlman K; McGill Group for Suicide Studies, Douglas Mental Health University Institute, Verdun, QC, Canada; Integrated Program in Neuroscience, McGill University, Montreal, QC, Canada., Fakhfouri G; Department of Psychiatry, Douglas Hospital, McGill University, Montreal, QC, Canada., Mpai R; McGill Group for Suicide Studies, Douglas Mental Health University Institute, Verdun, QC, Canada; Integrated Program in Neuroscience, McGill University, Montreal, QC, Canada., Richard VR; Segal Cancer Proteomics Centre, Lady Davis Institute for Medical Research, Jewish General Hospital, McGill University, Montréal, QC, Canada., Hercher C; McGill Group for Suicide Studies, Douglas Mental Health University Institute, Verdun, QC, Canada; Integrated Program in Neuroscience, McGill University, Montreal, QC, Canada., Penney L; Department of Psychiatry, Douglas Hospital, McGill University, Montreal, QC, Canada., Davoli MA; McGill Group for Suicide Studies, Douglas Mental Health University Institute, Verdun, QC, Canada; Department of Psychiatry, McGill University, Montreal, QC, Canada., Nagy C; McGill Group for Suicide Studies, Douglas Mental Health University Institute, Verdun, QC, Canada; Department of Psychiatry, McGill University, Montreal, QC, Canada; Integrated Program in Neuroscience, McGill University, Montreal, QC, Canada., Zahedi RP; Department of Internal Medicine, University of Manitoba, Winnipeg, MB, Canada; Manitoba Centre for Proteomics and Systems Biology, University of Manitoba, Winnipeg, MB, Canada; Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, MB, Canada; CancerCare Manitoba Research Institute, Winnipeg, MB, Canada., Borchers CH; Segal Cancer Proteomics Centre, Lady Davis Institute for Medical Research, Jewish General Hospital, McGill University, Montréal, QC, Canada; Gerald Bronfman Department of Oncology, McGill University, Montréal, Québec, Canada; Department of Pathology, McGill University, Montréal, QC, Canada; Department of Experimental Medicine, McGill University, Montreal, QC, Canada., Giros B; Department of Psychiatry, Douglas Hospital, McGill University, Montreal, QC, Canada., Turecki G; McGill Group for Suicide Studies, Douglas Mental Health University Institute, Verdun, QC, Canada; Department of Psychiatry, McGill University, Montreal, QC, Canada; Integrated Program in Neuroscience, McGill University, Montreal, QC, Canada., Mechawar N; McGill Group for Suicide Studies, Douglas Mental Health University Institute, Verdun, QC, Canada; Department of Psychiatry, McGill University, Montreal, QC, Canada; Integrated Program in Neuroscience, McGill University, Montreal, QC, Canada. Electronic address: naguib.mechawar@mcgill.ca.
Jazyk: angličtina
Zdroj: Brain, behavior, and immunity [Brain Behav Immun] 2024 Nov; Vol. 122, pp. 110-121. Date of Electronic Publication: 2024 Aug 14.
DOI: 10.1016/j.bbi.2024.08.016
Abstrakt: The olfactory bulb (OB), a major structure of the limbic system, has been understudied in human investigations of psychopathologies such as depression. To explore more directly the molecular features of the OB in depression, a global comparative proteome analysis was carried out with human post-mortem OB samples from 11 males having suffered from depression and 12 healthy controls. We identified 188 differentially abundant proteins (with adjusted p < 0.05) between depressed cases and controls. Gene ontology and gene enrichment analyses suggested that these proteins are involved in biological processes including the complement and coagulation cascades. Cell type enrichment analysis displayed a significant reduction in several canonical astrocytic proteins in OBs from depressed patients. Furthermore, using RNA-fluorescence in-situ hybridization, we observed a decrease in the percentage of ALDH1L1 + cells expressing canonical astrocytic markers including ALDOC, NFIA, GJA1 (connexin 43) and SLC1A3 (EAAT1). These results are consistent with previous reports of downregulated astrocytic marker expression in other brain regions in depressed patients. We also conducted a comparative phosphoproteomic analysis of OB samples and found a dysregulation of proteins involved in neuronal and astrocytic functions. To determine whether OB astrocytic abnormalities is specific to humans, we also performed proteomics on the OB of socially defeated male mice, a commonly used model of depression. Cell-type specific analysis revealed that in socially defeated animals, the most striking OB protein alterations were associated with oligodendrocyte-lineage cells rather than with astrocytes, highlighting an important species difference. Overall, this study further highlights cerebral astrocytic abnormalities as a consistent feature of depression in humans.
Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [CHB is the CSO of MRM Proteomics Inc., and the VP of Proteomics at Molecular You. RPZ is CEO of MRM Proteomics. The remaining authors declare no conflict of interest].
(Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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