Role of microglial m1/m2 polarization in relapse and remission of psychiatric disorders and diseases
Open accessAbstract
Psychiatric disorders such as schizophrenia and major depressive disorder were thought to be caused by neurotransmitter abnormalities. Patients with these disorders often experience relapse and remission; however the underlying molecular mechanisms of relapse and remission still remain unclear. Recent advanced immunological analyses have revealed that M1/M2 polarization of macrophages plays an important role in controlling the balance between promotion and suppression in inflammation. Microglial cells share certain characteristics with macrophages and contribute to immune-surveillance in the central nervous system (CNS). In this review, we summarize immunoregulatory functions of microglia and discuss a possible role of microglial M1/M2 polarization in relapse and remission of psychiatric disorders and diseases. M1 polarized microglia can produce pro-inflammatory cytokines, reactive oxygen species, and nitric oxide, suggesting that these molecules contribute to dysfunction of neural network in the CNS. Alternatively, M2 polarized microglia express cytokines and receptors that are implicated in inhibiting inflammation and restoring homeostasis. Based on these aspects, we propose a possibility that M1 and M2 microglia are related to relapse and remission, respectively in psychiatric disorders and diseases. Consequently, a target molecule skewing M2 polarization of microglia may provide beneficial therapies for these disorders and diseases in the CNS.
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Sex differences in the immune system affect the brain, and are seen most notably in the functions of astroglia and microglia.
“Sex differences in the immune system affect the brain, and are seen most notably in the functions of astroglia and microglia, both brain cells that reportedly play a role in psychiatric disease (80).”
From Where Sex Meets Gender: How Sex and Gender Come Together to Cause Sex Differences in Mental Illness (2022) · cites this paper as [80]
The Introduction and section 4 (Major Depressive Disorder; page unavailable) discuss microglial and astrocyte functions in psychiatric disease. But the paper does not address sex differences in immune function or say that their effects on the brain are most notable in astroglia and microglia (searched: sex differences, gender differences, male, female). (LLM, conf=0.84)
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The role of inflammation and microglial activation in the pathophysiology of psychiatric disorders
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Imaging robust microglial activation after lipopolysaccharide administration in humans with PET
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Diversity and plasticity of microglial cells in psychiatric and neurological disorders
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Self-citationZhang, C., Zhang, Y.-P., Li, Y.-Y., Liu, B.-P., Wang, H.-Y., Li, K.-W., Zhao, S., & Song, C. (2019) · Behavioural Brain Research · doi:10.1016/j.bbr.2018.07.001 · Cited by 172 · see citing works
Inflammation within the neurovascular unit: Focus on microglia for stroke injury and recovery
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Where Sex Meets Gender: How Sex and Gender Come Together to Cause Sex Differences in Mental Illness
Christiansen, D. M., McCarthy, M. M., & Seeman, M. V. (2022) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2022.856436 · Cited by 65 · see citing works
“Sex differences in the immune system affect the brain, and are seen most notably in the functions of astroglia and microglia, both brain cells that reportedly play a role in psychiatric disease (80).”
BackgroundNakagawa, Y., & Yamada, S. (2023) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.122.001482 · Cited by 20 · see citing works
Self-citationPatel, S., Govindarajan, V., Chakravarty, S., & Dubey, N. (2024) · International Immunopharmacology · doi:10.1016/j.intimp.2024.113326 · Cited by 10 · see citing works
- Authors
- Nakagawa, Y., & Chiba, K.
- Affiliations
- Tanabe Pharma Corporation (Japan) (JP)
- Corresponding author
- Chiba, Kenji
- Venue
- Pharmaceuticals
- Publisher
- MDPI AG
- Published
- 2014-11-25
- Volume
- 7
- Issue
- 12
- Pages
- 1028-1048
- ISSN
- 1424-8247 (ISSN-L)
- PMC
- PMC4276905
- OpenAlex
- W2125393554
- Cited by
- 215
- References
- 136
- Citations by year
- 2026: 12 · 2025: 25 · 2024: 21 · 2023: 16 · 2022: 17 · 2021: 28 · 2020: 19 · 2019: 21 · 2018: 14 · 2017: 15 · 2016: 16 · 2015: 11
- FWCI
- 1.13
- Type
- journal article
- Language
- en
- Open access
- gold
- dx.doi.org
- Licence
- Locations
- Pharmaceuticals (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Keywords
- relapse and remission, mental illness, schizophrenia, major depressive disorder, neuroinflammation, inflammatory cytokines, reactive oxygen species, nitric oxide, M2 polarization, neuroimmune regulation, CNS homeostasis
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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