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Insights into Macrophage Heterogeneity and Cytokine-Induced Neuroinflammation in Major Depressive Disorder

Dey, Adwitia, Hankey Giblin, Pamela A.·2018·Pharmaceuticals
DOI 10.3390/ph11030064PMC PMC6160985
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Abstract

Over 350 million individuals suffer from depression, a psychiatric illness classified as major depressive disorder (MDD) with symptoms that include a loss of interest or pleasure in life accompanied by depressed mood. The present understanding of major depressive disorder does not encompass a systematic characterization of the neurobiological processes that drive the behavioral physiology in patients diagnosed with major depressive disorder. Psychiatric illness is a complex intersection between genetics, physiology, immunology and environmental stress. The increased attention to the relevance of depression has led to new discoveries that highlight the biological significance of ‘neuroinflammation’ and immunity underlying a spectrum of psychiatric illnesses. The process of neuroinflammation involves sentinel immune cells in the central nervous system (CNS). The activation and polarization of microglia, CNS-resident macrophages, modulates the production and secretion of pro-inflammatory cytokines implicated in the etiology of major depressive disorder, and this phenomenon has been aptly titled the ‘macrophage theory of depression’. Of particular interest are three hallmark cytokines, IL-6, TNFα and IL-1β, which have been studied extensively in basic research, cell-receptor signaling and drug development. The field of inflammasome-mediated neuroinflammation is an emerging area of MDD research that is providing new cellular insight into how macrophages mechanistically support cytokine-associated neuropathology, particularly in the case of IL-1β-associated inflammation in MDD. With the increasing number of individuals identified with depression, a comprehensive understanding of macrophage-cytokine signaling pathways in the CNS in depression is necessary for developing effective anti-depressant therapeutics.

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  • Activation and polarization of microglia are regulated by the brain-derived microenvironment.

    “Based on the fact that the activation and polarization of microglia are regulated by the brain-derived microenvironment [19], we first isolated exosomes from MDD patients, and examined their function on microglia polarization.”

    From Neuron secrete exosomes containing miR-9-5p to promote polarization of M1 microglia in depression (2022) · cites this paper as [19]

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Cited by

Sorted by citations

Authors
Dey, A., & Hankey Giblin, P. A.
Affiliations
Center for Molecular Immunology and Infectious Diseases, The Pennsylvania State University, University Park, State College, PA 16802, USA
ORCID
Dey, Adwitia
Venue
Pharmaceuticals
Publisher
MDPI AG
Published
2018-06-25
Volume
11
Issue
3
Pages
64
ISSN
1424-8247
DOI
10.3390/ph11030064
PMC
PMC6160985
Cited by
65
References
19
Language
en
Licence
creativecommons.org/licenses/by/4.0/ (vor)

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