期刊
GLIA
卷 70, 期 3, 页码 451-465出版社
WILEY
DOI: 10.1002/glia.24114
关键词
complement; microglia engulfment; synapse elimination; visual system
资金
- National Alliance for Research on Schizophrenia and Depression [25248]
- National Cancer Institute [P30CA54174]
- National Institute of Neurological Disorders and Stroke [R01NS112389]
- National Institute on Aging [P01AG19316, R01AG060148]
- William and Ella Owens Medical Research Foundation
- UTHSCSA
- University of Texas System
- UTHSCSA Department of Pharmacology
- [NH21500221]
The study reveals that the classical complement pathway regulates microglia-mediated synapse elimination in the visual thalamus but does not affect the primary visual cortex during early development of the central nervous system.
The classical complement cascade mediates synapse elimination in the visual thalamus during early brain development. However, whether the primary visual cortex also undergoes complement-mediated synapse elimination during early visual system development remains unknown. Here, we examined microglia-mediated synapse elimination in the visual thalamus and the primary visual cortex of early postnatal C1q and SRPX2 knockout mice. In the lateral geniculate nucleus, deletion of C1q caused a persistent decrease in synapse elimination and microglial synapse engulfment, while deletion of SRPX2 caused a transient increase in the same readouts. In the C1q-SRPX2 double knockout mice, the C1q knockout phenotypes were dominant over the SRPX2 knockout phenotypes, a result which is consistent with SRPX2 being an inhibitor of C1q. We found that genetic deletion of either C1q or SRPX2 did not affect synapse elimination or microglial engulfment of synapses in layer 4 of the primary visual cortex in early brain development. Together, these results show that the classical complement pathway regulates microglia-mediated synapse elimination in the visual thalamus but not the visual cortex during early development of the central nervous system.
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