Biology subjects

Barasa, M. N.

Publications and source records attributed to Barasa, M. N..

2 recordsLinked to original sources

bioRxiv2026

Microglia detection and phagocytosis of dying neurons is regulated by CX3CR1

Neuronal cell death is a hallmark of many neurodegenerative diseases. Effective detection and clearance of cell debris generated during cell death events is essential to prevent a degenerative cascade. Brain resident microglia are responsible for performing these functions through complex cell-cell signaling involving both "find-me" and "eat-me" cues. To examine microglial responses to neuronal cell death in vivo, we investigated neuron/microglia CX3CL1/CX3CR1 signaling using intravital optical imaging in mouse cortex and a single-cell ablation technique called 2Phatal. We find that CX3CL1 aggregates as puncta on microglia and that this pattern is maintained when microglia engulf dying neurons. Additionally, disruption of this signaling via Cx3cr1 deletion when both few and many neurons are dying leads to delayed cell corpse clearance, partly due to a delay in microglial engagement with the dying cells. Overall, our work uncovers a precise role for CX3CL1/CX3CR1 signaling in regulating the microglial response to dying neocortical neurons.

neuroscience↗

bioRxiv2023

Microglial phagocytosis of single dying oligodendrocytes is mediated by CX3CR1 but not MERTK

Oligodendrocyte death is common in aging and neurodegenerative diseases. In these conditions, single dying oligodendrocytes must be efficiently removed to allow remyelination and prevent a feed-forward degenerative cascade. Here we used a single-cell cortical demyelination model combined with longitudinal intravital imaging of dual-labeled transgenic mice to investigate the cellular dynamics underlying how brain resident microglia remove these cellular debris. Following phagocytic engagement, single microglia cleared the targeted oligodendrocyte and its myelin sheaths in one day via a precise, rapid, and stereotyped sequence. Deletion of the fractalkine receptor, CX3CR1, delayed microglia engagement with the cell soma but unexpectedly did not affect the clearance of myelin sheaths. Furthermore, and in contrast to previous reports in other demyelination models, deletion of the phosphatidylserine receptor, MERTK, did not affect oligodendrocyte or myelin sheath clearance. Thus, distinct molecular signals are used to detect, engage, and clear sub-compartments of dying oligodendrocytes to maintain tissue homeostasis.

neuroscience↗