| First Author | Xie M | Year | 2025 |
| Journal | Immunity | Volume | 58 |
| Issue | 12 | Pages | 3113-3129.e8 |
| PubMed ID | 40975067 | Mgi Jnum | J:382328 |
| Mgi Id | MGI:8269195 | Doi | 10.1016/j.immuni.2025.08.016 |
| Citation | Xie M, et al. (2025) Rod-shaped microglia interact with neuronal dendrites to attenuate cortical excitability during TDP-43-related neurodegeneration. Immunity 58(12):3113-3129.e8 |
| abstractText | Microglia, the principal immune cells of the central nervous system, have emerged as important players in sensing and regulating neuronal activity. While microglial activation is a hallmark in neurodegeneration, the specific role of microglia in disease-related cortical excitability remains unknown. Utilizing multichannel probe recordings and longitudinal in vivo calcium imaging, we observed neuronal hyperactivity at the initial stage of disease progression in a mouse model of TAR DNA-binding protein 43 (TDP-43) neurodegeneration (rNLS8, regulated nuclear localization sequence-deleted human TDP-43 transgenic mouse model). Spatial and single-cell RNA sequencing revealed a specific subpopulation of microglia, rod-shaped microglia, with a distinct morphology and direct response to cortical hyperactivity. Rod-shaped microglia predominantly interacted with neuronal dendrites and remodeled excitatory synaptic inputs to attenuate motor cortical hyperactivity. Triggering receptor expressed on myeloid cells 2 (TREM2) deficiency led to a marked reduction of rod-shaped microglia accompanied by increased neuronal activity in rNLS8 mice. Together, our results suggest that rod-shaped microglia play a neuroprotective role by attenuating cortical hyperexcitability in TDP-43-related neurodegeneration. |
