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Microglia promote maladaptive plasticity in autonomic circuitry after spinal cord injury in mice
Brennan FH, Swarts EA, Kigerl KA, Mifflin KA, Guan Z, Noble BT, Wang Y, Witcher KG et al.. Science translational medicine, 2024-06-12
Topic: Brain proteins, microglia and lab models
Robust structural remodeling and synaptic plasticity occurs within spinal autonomic circuitry after severe high-level spinal cord injury (SCI). As a result, normally innocuous visceral or somatic stimuli elicit uncontrolled activation of spinal sympathetic reflexes that contribute to systemic disease and organ-specific pathology. How hyperexcitable sympathetic circuitry forms is unknown, but local cues from neighboring glia likely help mold these maladaptive neuronal networks. Here, we used a mouse model of SCI to show that microglia surrounded active glutamatergic interneurons and subsequently coordinated multi-segmental excitatory synaptogenesis and expansion of sympathetic networks that control immune, neuroendocrine, and cardiovascular functions. Depleting microglia during critical periods of circuit remodeling after SCI prevented maladaptive synaptic and structural plasticity in autonomic networks, decreased the frequency and severity of autonomic dysreflexia, and prevented SCI-induced immunosuppression. Forced turnover of microglia in microglia-depleted mice restored structural and functional indices of pathological dysautonomia, providing further evidence that microglia are key effectors of autonomic plasticity. Additional data show that microglia-dependent autonomic plasticity required expression of triggering receptor expressed on myeloid cells 2 (Trem2) and α2δ-1-dependent synaptogenesis. These data suggest that microglia are primary effectors of autonomic neuroplasticity and dysautonomia after SCI in mice. Manipulating microglia may be a strategy to limit autonomic complications after SCI or other forms of neurologic disease.
Key findings
- As a result, normally innocuous visceral or somatic stimuli elicit uncontrolled activation of spinal sympathetic reflexes that contribute to systemic disease and organ-specific pathology.
- These data suggest that microglia are primary effectors of autonomic neuroplasticity and dysautonomia after SCI in mice.
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Study details
- Evidence strengthLow
How this study scored 41/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported and randomised / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multi-centre collaboration, so those were left out: it earned 24 of the 58 points we could judge it on, which is 41 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Science translational medicine) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 4 / 5 | 2024 — within 3 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Laboratory or animal study (title names “mice”) — scores zero |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 38865485) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 24 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 24 of the 58 points we could judge it on is 41 out of 100. |
| Total | 41 / 100 | — |
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Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Brennan, F. H., Swarts, E. A., Kigerl, K. A., Mifflin, K. A., Guan, Z., Noble, B. T., et al. (2024). Microglia promote maladaptive plasticity in autonomic circuitry after spinal cord injury in mice. Science translational medicine. https://doi.org/10.1126/scitranslmed.adi3259
Vancouver
Brennan FH, Swarts EA, Kigerl KA, Mifflin KA, Guan Z, Noble BT, et al. Microglia promote maladaptive plasticity in autonomic circuitry after spinal cord injury in mice. Science translational medicine. 2024. doi:10.1126/scitranslmed.adi3259. PMID: 38865485.
BibTeX
@article{brennan2024-38865485,
author = {Brennan, F. H. and Swarts, E. A. and Kigerl, K. A. and Mifflin, K. A. and Guan, Z. and Noble, B. T. and Wang, Y. and Witcher, K. G. and others},
title = {{Microglia promote maladaptive plasticity in autonomic circuitry after spinal cord injury in mice}},
journal = {Science translational medicine},
year = {2024},
doi = {10.1126/scitranslmed.adi3259},
pmid = {38865485},
url = {https://doi.org/10.1126/scitranslmed.adi3259}
}
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