期刊
CEREBRAL CORTEX
卷 29, 期 4, 页码 1634-1643出版社
OXFORD UNIV PRESS INC
DOI: 10.1093/cercor/bhy061
关键词
dendritic spine; microglia; pyramidal cell; schizophrenia; synaptic pruning
资金
- National Institute of Mental Health [MH077298]
- National Institute of Child Health and Development [P30HD15052]
- NIH grant National Cancer Institute [CA68485]
- NIH grant National Institute of Diabetes and Digestive and Kidney Diseases [DK20593, DK58404, DK59637]
- NIH grant National Eye Institute [EY08126]
Exaggerated synaptic elimination in the prefrontal cortex (PFC) during adolescence has been suggested to contribute to the neuropathological changes of schizophrenia. Recent data indicate that microglia (MG) sculpt synapses during early postnatal development. However, it is not known if MG contribute to the structural maturation of the PFC, which has a protracted postnatal development. We determined if MG are involved in developmentally specific synapse elimination in the PFC, focusing on adolescence. Layer 5 PFC pyramidal cells (PCs) were intracellularly filled with Lucifer Yellow for dendritic spine measurements in postnatal day (P) 24, P30, P35, P39, and P50 rats. In the contralateral PFC we evaluated if MG engulfed presynaptic (glutamatergic) and postsynaptic (dendritic spines) elements. Dendritic spine density increased from P24 to P35, when spine density peaked. There was a significant increase in MG engulfment of spines at P39 relative to earlier ages; this subsided by P50. MG also phagocytosed presynaptic glutamatergic terminals. These data indicate that MG transiently prune synapses of PFC PCs during adolescence, when the symptoms of schizophrenia typically first appear. An increase in MG-mediated synaptic remodeling of PFC PCs may contribute to the structural changes observed in schizophrenia.
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