Journal
NEURON
Volume 109, Issue 16, Pages 2573-+Publisher
CELL PRESS
DOI: 10.1016/j.neuron.2021.06.012
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Funding
- National Natural Science Foundation of China [32025017, 81870877, 91849119, 32000717]
- Collaborative Innovation Program of Hefei Science Center, Chinese Academy of Sciences (CAS) [2019HSC-CIP003]
- Fundamental Research Funds for the Central Universities [WK9110000059, WK2070210004]
- Shanghai Municipal Science and Technology Major Project [2018SHZDZX01]
- Scientific Research of BSKY from Anhui Medical University [XJ201809]
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Early-life inflammation can increase the risk for depression in later life by affecting the long-term neuronal spine engulfment capacity of microglia. Mouse studies have shown that depressive-like stress can increase microglial engulfment of specific neuronal spines, and inhibiting microglial activity may reduce depressive symptoms.
Early-life inflammation increases the risk for depression in later life. Here, we demonstrate how early-life inflammation causes adolescent depressive-like symptoms: by altering the long-term neuronal spine engulfment capacity of microglia. For mice exposed to lipopolysaccharide (LPS)-induced inflammation via the Toll-like receptor 4/NF-kappa B signaling pathway at postnatal day (P) 14, ongoing longitudinal imaging of the living brain revealed that later stress (delivered during adolescence on P45) increases the extent of microglial engulfment around anterior cingulate cortex (ACC) glutamatergic neuronal (ACC(Glu)) spines. When the ACC microglia of LPS-treated mice were deleted or chemically inhibited, the mice did not exhibit depressive-like behaviors during adolescence. Moreover, we show that the fractalkine receptor CX3CR1 mediates stress-induced engulfment of ACC(Glu) neuronal spines. Together, our findings establish that early-life inflammation causes dysregulation of microglial engulfment capacity, which encodes long-lasting maladaptation of ACC(Glu) neurons to stress, thus promoting development of depression-like symptoms during adolescence.
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