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Published on: August 13, 2020
TMEM119-defined brain macrophage phenotypes in a chronic stress model induced by corticosterone in male mice
Ryuichi Nakagawa1, Hiroyuki Nakashima2, Mayumi Sato1
1Department of Psychiatry, The National Defense Medical College, Saitama, Japan.
Abstract:
Microglia are crucial for brain immunity, and their phenotypic changes have been implicated in neuroinflammation and the development of depression and anxiety symptoms. The accurate characterization of these changes is challenging due to the interaction of microglia with the brain microenvironment and the presence of central nervous system (CNS)-resident macrophages that share common markers with microglia. Using the microglia-specific marker TMEM119 and bone marrow chimeric mice, we investigated the changes in microglial activity in mice exposed to chronic corticosterone, a widely used rodent model of stress-related behaviors. Flow cytometry analysis was used to identify TMEM119intermidiary (int), CD45low microglia and TMEM119high (hi), CD45int microglia. Notably, corticosterone exposure led to a significant increase in the number of TMEM119int, CD45low microglia, whereas the proportions of TMEM119hi, CD45int microglia remained unchanged. The increased forward and side scatter properties of TMEM119hi, CD45int microglia suggest increased intracellular granularity, which may reflect distinct phenotypic features of this previously overlooked cell population. Our finding of an increased population of TMEM119hi, CD45int microglia may reflect a stress-adapted phenotype similar to that of clinical depression.
Insights
Stress impacts brain immunity by altering microglia. Chronic stress increased a specific microglial population (TMEM119hi, CD45int), potentially indicating a stress-adapted phenotype linked to depression.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Microglia are key to brain immunity, with altered phenotypes linked to neuroinflammation, depression, and anxiety.
- Distinguishing microglia from CNS-resident macrophages is challenging due to shared markers.
Purpose of the Study:
- To investigate microglial phenotypic changes in response to chronic stress using a rodent model.
- To characterize specific microglial populations using TMEM119 and CD45 markers.
Main Methods:
- Utilized bone marrow chimeric mice and chronic corticosterone exposure to model stress.
- Employed flow cytometry to analyze microglia populations, specifically TMEM119int, CD45low and TMEM119hi, CD45int cells.
Main Results:
- Chronic corticosterone exposure significantly increased TMEM119int, CD45low microglia.
- A distinct population, TMEM119hi, CD45int microglia, showed increased granularity, suggesting unique phenotypic features.
- The proportion of TMEM119hi, CD45int microglia remained unchanged but exhibited altered scatter properties.
Conclusions:
- Chronic stress induces specific changes in microglial populations.
- The observed increase in TMEM119hi, CD45int microglia with enhanced granularity may represent a stress-adapted phenotype.
- This phenotype could be relevant to understanding depression and anxiety symptoms associated with stress.
