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Published on: September 29, 2021
Basolateral Amygdala Reactive Microglia May Contribute to Synaptic Impairment and Depressive-Like Behavior in Mice
Li Jiang1, Jing Hao1, Xu-Li Yang1
1Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, 321 Zhongshan Road, Nanjing, 210008, China.
Abstract:
Anxiety and depression induced by cancer-related pain disturb quality of life and willingness to survive. As a component of the limbic system, the basolateral amygdala (BLA) is critical for processing negative emotions. The reactive microglial engulfment of synapses may promote depression during adolescence. However, whether microglia phagocytose synapses to mediate cancer pain-induced depression remains unclear. The present study established a bone cancer-pain model to investigate the association between dendritic spine synapses and depressive-like behavior and explore the phagocytic function of microglia in the BLA. We found that tumor-bearing mice experienced postoperative pain-related depression, and their BLAs exhibited reactive microglia, as well as phagocytic synapses. The microglial inhibitor minocycline effectively mitigated depressive behavior, synaptic damage, and the phagocytic function of microglia. Our study implicates microglia-mediated synaptic loss in the BLA may act as the pathological basis of depressive-like behavior in bone cancer pain model.
Insights
Cancer pain triggers depression by causing microglia to engulf synapses in the basolateral amygdala (BLA). Inhibiting microglia reduced depressive behavior and synaptic loss, suggesting a new therapeutic target for cancer pain-induced depression.
Area of Science:
- Neuroscience
- Oncology
- Immunology
Background:
- Cancer-related pain significantly impacts patient quality of life and survival by inducing anxiety and depression.
- The basolateral amygdala (BLA), a key limbic system component, processes negative emotions, and its dysfunction is linked to depression.
- Microglial engulfment of synapses is implicated in adolescent depression, but its role in cancer pain-induced depression is unknown.
Purpose of the Study:
- To investigate the link between dendritic spine synapses, depressive-like behavior, and microglial function in the BLA of a bone cancer pain model.
- To explore the role of microglia-mediated synaptic loss in the pathology of cancer pain-induced depression.
Main Methods:
- Establishment of a bone cancer pain mouse model.
- Assessment of depressive-like behavior in tumor-bearing mice.
- Investigation of microglial activity and synaptic changes within the BLA.
- Administration of the microglial inhibitor minocycline.
Main Results:
- Tumor-bearing mice exhibited depressive-like behavior and pain.
- Reactive microglia and phagocytic synapses were observed in the BLA of these mice.
- Minocycline treatment alleviated depressive behavior, reduced synaptic damage, and decreased microglial phagocytic activity.
Conclusions:
- Microglia-mediated synaptic loss in the BLA is a key pathological mechanism underlying depressive-like behavior in bone cancer pain.
- Targeting microglial function presents a potential therapeutic strategy for managing depression associated with cancer pain.
