| First Author | Lv Z | Year | 2024 |
| Journal | Neuron | Volume | 112 |
| Issue | 5 | Pages | 740-754.e7 |
| PubMed ID | 38295790 | Mgi Jnum | J:346141 |
| Mgi Id | MGI:7614088 | Doi | 10.1016/j.neuron.2023.12.003 |
| Citation | Lv Z, et al. (2024) Clearance of beta-amyloid and synapses by the optogenetic depolarization of microglia is complement selective. Neuron 112(5):740-754.e7 |
| abstractText | Microglia actively monitor the neighboring brain microenvironments and constantly contact synapses with their unique ramified processes. In neurodegenerative diseases, including Alzheimer's disease (AD), microglia undergo morphological and functional alterations. Whether the direct manipulation of microglia can selectively or concurrently modulate synaptic function and the response to disease-associated factors remains elusive. Here, we employ optogenetic methods to stimulate microglia in vitro and in vivo. Membrane depolarization rapidly changes microglia morphology and leads to enhanced phagocytosis. We found that the optogenetic stimulation of microglia can efficiently promote beta-amyloid (Abeta) clearance in the brain parenchyma, but it can also enhance synapse elimination. Importantly, the inhibition of C1q selectively prevents synapse loss induced by microglia depolarization but does not affect Abeta clearance. Our data reveal independent microglia-mediated phagocytosis pathways toward Abeta and synapses. Our results also shed light on a synergistic strategy of depolarizing microglia and inhibiting complement functions for the clearance of Abeta while sparing synapses. |
