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Microglia promote maladaptive plasticity in autonomic circuitry after spinal cord injury in mice.
- Source :
- Science Translational Medicine; 6/12/2024, Vol. 16 Issue 751, p1-17, 17p
- Publication Year :
- 2024
-
Abstract
- 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. Editor's summary: Spinal cord injuries (SCIs) above the mid-thoracic vertebrae disrupt central control over spinal autonomic circuits. The cellular drivers of the subsequent circuit remodeling that can lead to autonomic dysfunctions remain to be identified. Here, Brennan et al. used a mouse model of thoracic SCI and demonstrated that microglia depletion prevented SCI-associated autonomic circuit expansion as well as neuroendocrine dysregulation, immune dysfunction, and autonomic dysreflexia (AD). These results identify microglia as potential target to prevent maladaptive autonomic circuit remodeling. —Daniela Neuhofer [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 19466234
- Volume :
- 16
- Issue :
- 751
- Database :
- Complementary Index
- Journal :
- Science Translational Medicine
- Publication Type :
- Academic Journal
- Accession number :
- 177817586
- Full Text :
- https://doi.org/10.1126/scitranslmed.adi3259