The DOI matches its Crossref record; 74 of the 76 references it cites were found in a registry or an index.
Dendritic remodeling of D1 neurons by RhoA/Rho-kinase mediates depression-like behavior
Open accessAbstract
Depression alters the structure and function of brain reward circuitry. Preclinical evidence suggests that medium spiny neurons (MSNs) in the nucleus accumbens (NAc) undergo structural plasticity; however, the molecular mechanism and behavioral significance is poorly understood. Here we report that atrophy of D1, but not D2 receptor containing MSNs is strongly associated with social avoidance in mice subject to social defeat stress. D1-MSN atrophy is caused by cell-type specific upregulation of the GTPase RhoA and its effector Rho-kinase. Pharmacologic and genetic reduction of activated RhoA prevents depressive outcomes to stress by preventing loss of D1-MSN dendritic arbor. Pharmacologic and genetic promotion of activated RhoA enhances depressive outcomes by reducing D1-MSN dendritic arbor and is sufficient to promote depressive-like behaviors in the absence of stress. Chronic treatment with Rho-kinase inhibitor Y-27632 after chronic social defeat stress reverses depression-like behaviors by restoring D1-MSN dendritic complexity. Taken together, our data indicate functional roles for RhoA and Rho-kinase in mediating depression-like behaviors via dendritic remodeling of NAc D1-MSNs and may prove a useful target for new depression therapeutics.
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In the citing paper
“Susceptibility to chronic social defeat stress is accompanied by atrophy of MSN dendrites, specifically in D1 MSNs and not D2 MSNs, and a corresponding loss of dendritic spines [226,234,235].”
From Plasticity of synapses and reward circuit function in the genesis and treatment of depression (2023) · cites this paper as [235]
In the citing paper
“Susceptibility to chronic social defeat stress is accompanied by atrophy of MSN dendrites, specifically in D1 MSNs and not D2 MSNs, and a corresponding loss of dendritic spines [226,234,235].”
From Plasticity of synapses and reward circuit function in the genesis and treatment of depression (2023) · cites this paper as [235]
In the citing paper
“The GTPase RhoA, which negatively regulates dendritic complexity, is increased specifically in D1-MSNs of susceptible mice [138].”
From The molecular and cellular mechanisms of depression: a focus on reward circuitry (2019) · cites this paper as [138]
In the citing paper
“The GTPase RhoA, which negatively regulates dendritic complexity, is increased specifically in D1-MSNs of susceptible mice [138].”
From The molecular and cellular mechanisms of depression: a focus on reward circuitry (2019) · cites this paper as [138]
In the citing paper
“After CSDS, inhibiting downstream effector Rho-kinase reverses social withdrawal and forced-swim immobility [138].”
From The molecular and cellular mechanisms of depression: a focus on reward circuitry (2019) · cites this paper as [138]
In the citing paper
“Upregulation of RhoA in D1-MSNs either by Egr3 overexpression or RhoA over-expression promotes stress susceptibility [88, 138].”
From The molecular and cellular mechanisms of depression: a focus on reward circuitry (2019) · cites this paper as [138]
In the citing paper
“RhoA is transcriptionally regulated by Egr3 [88] and in stress-naive mice, increased RhoA in D1-MSNs decreases sucrose preference in males, grooming behavior in females, and forced-swim immobility.”
From The molecular and cellular mechanisms of depression: a focus on reward circuitry (2019) · cites this paper as [138]
In the citing paper
“Reduced D1-MSN complexity is sufficient to drive CSDS-susceptibility [88, 138].”
From The molecular and cellular mechanisms of depression: a focus on reward circuitry (2019) · cites this paper as [138]
In the citing paper
“The mechanism underlying structural plasticity of MSNs in CSDS is altered expression and activity of Rho GTPases [88, 89, 138, 141].”
From The molecular and cellular mechanisms of depression: a focus on reward circuitry (2019) · cites this paper as [138]
In the citing paper
“In the NAc, dendritic complexity of D1-, but not D2-MSNs, is reduced in CSDS-susceptible mice.”
From The molecular and cellular mechanisms of depression: a focus on reward circuitry (2019) · cites this paper as [138]
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Cites
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Modulation of Striatal Projection Systems by Dopamine
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A standardized protocol for repeated social defeat stress in mice
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The neostriatal mosaic: multiple levels of compartmental organization
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Rapid regulation of depression-related behaviours by control of midbrain dopamine neurons
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Cited by
Sorted by citations
Castro, D. C., & Bruchas, M. R. (2019) · Neuron · doi:10.1016/j.neuron.2019.03.003 · Cited by 306
The molecular and cellular mechanisms of depression: a focus on reward circuitry
Fox, M. E., & Lobo, M. K. (2019) · Molecular Psychiatry · doi:10.1038/s41380-019-0415-3 · Cited by 232
Self-citationMicroRNA mediators of early life stress vulnerability to depression and suicidal behavior
Allen, L., & Dwivedi, Y. (2019) · Molecular Psychiatry · doi:10.1038/s41380-019-0597-8 · Cited by 152
Gebara, E., Zanoletti, O., Ghosal, S., Grosse, J., Schneider, B. L., Knott, G. W., Astori, S., & Sandi, C. (2020) · Biological Psychiatry · doi:10.1016/j.biopsych.2020.12.003 · Cited by 152
Microglial deletion and inhibition alleviate behavior of post-traumatic stress disorder in mice
Li, S., Liao, Y., Dong, Y., Li, X., Li, J., Cheng, Y., Cheng, J., & Yuan, Z. (2021) · Journal of Neuroinflammation · doi:10.1186/s12974-020-02069-9 · Cited by 118
Metadata
- Authors
- Fox, M. E., Chandra, R., Menken, M. S., Larkin, E. J., Nam, H., Engeln, M., Francis, T. C., & Lobo, M. K.
- Affiliations
- University of Maryland, Baltimore (US)
- Corresponding author
- Lobo, Mary Kay
- Venue
- Molecular Psychiatry
- Published
- 2018-08-17
- Volume
- 25
- Issue
- 5
- Pages
- 1022-1034
- ISSN
- 1359-4184 (ISSN-L)
- 1476-5578
- PMC
- PMC6378138
- OpenAlex
- W2885753453
- Cited by
- 100
- References
- 76
- Citations by year
- 2026: 9 · 2025: 7 · 2024: 12 · 2023: 10 · 2022: 16 · 2021: 19 · 2020: 18 · 2019: 8 · 2018: 1
- FWCI
- 7.42
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (R01MH106500, F32MH116574)
- One Mind/ Janssen Rising Star Translational Research Award
- Topics
- Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- depression, RhoA, Rho kinase, dopamine D1 receptor, medium spiny neurons, nucleus accumbens, dendritic remodeling, dendritic atrophy, social defeat stress, social avoidance, Y-27632, structural plasticity, reward systems
- MeSH terms
- Animals, Dendrites, Depression, Male, Mice, Inbred C57BL, Mice, Transgenic, Neuronal Plasticity, Nucleus Accumbens, Receptors, Dopamine D1, Receptors, Dopamine D2, rhoA GTP-Binding Protein, Mice, rho-Associated Kinases
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