The DOI matches its Crossref record; 67 of the 67 references it cites were found in a registry or an index.
Stress-Induced Neuronal Colony Stimulating Factor 1 Provokes Microglia-Mediated Neuronal Remodeling and Depressive-like Behavior
Open accessAbstract
Background Chronic stress exposure causes neuronal atrophy and synaptic deficits in the medial prefrontal cortex (PFC), contributing to development of anxiety- and depressive-like behaviors. Concomitantly, microglia in the PFC undergo morphological and functional changes following stress exposure, suggesting that microglia contribute to synaptic deficits underlying behavioral consequences.Methods Male and female mice were exposed to chronic unpredictable stress (CUS) to examine the role of neuron-microglia interactions in the medial PFC during development of anxiety- and depressive-like behaviors. Thy1-GFP-M mice were used to assess microglia-mediated neuronal remodeling and dendritic spine density in the medial PFC. Viral-mediated knockdown of neuronal colony stimulating factor 1 (CSF1) was used to modulate microglia function and behavioral consequences after CUS.Results CUS promoted anxiety- and depressive-like behaviors that were associated with increased messenger RNA levels of CSF1 in the PFC. Increased CSF1 messenger RNA levels were also detected in the postmortem dorsolateral PFC of individuals with depression. Moreover, microglia isolated from the frontal cortex of mice exposed to CUS show elevated CSF1 receptor expression and increased phagocytosis of neuronal elements. Notably, functional alterations in microglia were more pronounced in male mice compared with female mice. These functional changes in microglia corresponded with reduced dendritic spine density on pyramidal neurons in layer 1 of the medial PFC. Viral-mediated knockdown of neuronal CSF1 in the medial PFC attenuated microglia-mediated neuronal remodeling and prevented behavioral deficits caused by CUS.Conclusions These findings revealed that stress-induced elevations in neuronal CSF1 provokes microglia-mediated neuronal remodeling in the medial PFC, contributing to synaptic deficits and development of anxiety- and depressive-like behavior.
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“Recent evidence demonstrates that chronic stress also leads to activation of microglia, the brain's resident immune cells, which engulf synapses on nearby pyramidal neurons and thereby contribute to neuronal atrophy 29 .”
From Neuroplasticity in cognitive and psychological mechanisms of depression: an integrative model (2020) · cites this paper as [29]
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“Microglia in CUS mice have enhanced colony stimulating factor 1 receptor expression and enhanced phagocytotic activity, paralleled by CSF1 elevations in postmortem MDD tissue [185].”
From The molecular and cellular mechanisms of depression: a focus on reward circuitry (2019) · cites this paper as [185]
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“Viral knockdown of neuronal Csf1 attenuates dendritic spine pruning on mPFC neurons and prevents stress-induced anhedonia and forced-swim immobility [185].”
From The molecular and cellular mechanisms of depression: a focus on reward circuitry (2019) · cites this paper as [185]
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“As microglia are the resident immune cells of the central nervous system (CNS) and microglial transcripts are upregulated after stress [185], they are an attractive linker between inflammation and depression in the brain.”
From The molecular and cellular mechanisms of depression: a focus on reward circuitry (2019) · cites this paper as [185]
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Woodburn, S. C., Bollinger, J. L., & Wohleb, E. S. (2021) · Journal of Neuroinflammation · doi:10.1186/s12974-021-02309-6 · Cited by 783
Self-citationNeuroplasticity in cognitive and psychological mechanisms of depression: an integrative model
Price, R. B., & Duman, R. (2020) · Molecular Psychiatry · doi:10.1038/s41380-019-0615-x · Cited by 739
Self-citationSex differences in stress-related alcohol use
Peltier, M. R., Verplaetse, T. L., Mineur, Y. S., Petrakis, I. L., Cosgrove, K., Picciotto, M. R., & McKee, S. A. (2019) · Neurobiology of Stress · doi:10.1016/j.ynstr.2019.100149 · Cited by 440
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Metadata
- Authors
- Wohleb, E. S., Terwilliger, R., Duman, C. H., & Duman, R. S.
- Affiliations
- Yale University (US)
- Corresponding author
- Wohleb, Eric S.
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2018-01
- Volume
- 83
- Issue
- 1
- Pages
- 38-49
- ISSN
- 0006-3223 (ISSN-L)
- PMC
- PMC6506225
- OpenAlex
- W2730743637
- Cited by
- 288
- References
- 67
- Citations by year
- 2026: 23 · 2025: 39 · 2024: 31 · 2023: 34 · 2022: 37 · 2021: 49 · 2020: 28 · 2019: 30 · 2018: 14
- FWCI
- 9.74
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Mental Health (R01MH093897, R37MH045481, R01MH045481)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- chronic unpredictable mild stress, colony-stimulating factor 1, microglia, neuronal remodeling, medial prefrontal cortex, depression-like behavior, anxiety-like behavior, dendritic spine density, synaptic deficits, CSF-1 receptor, microglial phagocytosis, sex differences, depression
- MeSH terms
- Animals, Anxiety, Chronic Disease, Depressive Disorder, Disease Models, Animal, Female, Male, Mice, Inbred C57BL, Mice, Transgenic, Neuronal Plasticity, Neurons, Phagocytosis, RNA, Messenger, Sex Characteristics, Stress, Psychological, Macrophage Colony-Stimulating Factor, Receptor, Macrophage Colony-Stimulating Factor, Prefrontal Cortex, Microglia, Uncertainty
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