2. Academic Validation
  3. Early-life inflammation promotes depressive symptoms in adolescence via microglial engulfment of dendritic spines

Early-life inflammation promotes depressive symptoms in adolescence via microglial engulfment of dendritic spines

  • Neuron. 2021 Aug 18;109(16):2573-2589.e9. doi: 10.1016/j.neuron.2021.06.012.
Peng Cao 1,  Changmao Chen 1,  An Liu 2,  Qinghong Shan 1,  Xia Zhu 1,  Chunhui Jia 1,  Xiaoqi Peng 1,  Mingjun Zhang 1,  Zahra Farzinpour 1,  Wenjie Zhou 1,  Haitao Wang 1,  Jiang-Ning Zhou 1,  Xiaoyuan Song 1,  Liecheng Wang 2,  Wenjuan Tao 2,  Changjian Zheng 3,  Yan Zhang 4,  Yu-Qiang Ding 5,  Yan Jin 6,  Lin Xu 7,  Zhi Zhang 8
Affiliations

Affiliations

  • 1 Department of Anesthesiology, The First Affiliated Hospital of USTC, Hefei National Laboratory for Physical Sciences at the Microscale, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230036, China.
  • 2 Department of Physiology, School of Basic Medical Sciences, Anhui Medical University, Hefei 230022, China.
  • 3 Department of Anesthesiology, the First Affiliated Hospital of Wannan Medical College, Wuhu 241002, China.
  • 4 Stroke Center & Department of Neurology, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230036, China.
  • 5 State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, and Department of Laboratory Animal Science, Fudan University, Shanghai 200032, China.
  • 6 Department of Anesthesiology, The First Affiliated Hospital of USTC, Hefei National Laboratory for Physical Sciences at the Microscale, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230036, China. Electronic address: jinyan@ustc.edu.cn.
  • 7 Key Laboratory of Animal Models and Human Disease Mechanisms, and Laboratory of Learning and Memory, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China. Electronic address: lxu@vip.163.com.
  • 8 Department of Anesthesiology, The First Affiliated Hospital of USTC, Hefei National Laboratory for Physical Sciences at the Microscale, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230036, China. Electronic address: zhizhang@ustc.edu.cn.
PMID: 34233151 DOI: 10.1016/j.neuron.2021.06.012
Abstract

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-κB 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 (ACCGlu) 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 ACCGlu neuronal spines. Together, our findings establish that early-life inflammation causes dysregulation of microglial engulfment capacity, which encodes long-lasting maladaptation of ACCGlu neurons to stress, thus promoting development of depression-like symptoms during adolescence.

Keywords

ACC; calcium imaging; chemogenetics; dendritic spines; depressive symptoms; early-life inflammation; microglial engulfment; neuronal activity.

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