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A Chronic Immobilization Stress Protocol for Inducing Depression-Like Behavior in Mice
Published on: May 15, 2019
Chronic foot-shock stress potentiates the influx of bone marrow-derived microglia into hippocampus
Marie Brevet1, Hideto Kojima, Akihiro Asakawa
1Department of Pathology, CHU Amiens, Amiens, France. brevetm@mskcc.org
Abstract:
For several years, a new population of microglia derived from bone marrow has been described in multiple settings such as infection, trauma, and neurodegenerative disease. The aim of this study was to investigate the migration of bone marrow-derived cells to the brain parenchyma after stress exposure. Stress exposure was performed in mice that had received bone marrow transplantation from GFP mice, allowing identification of blood-derived elements within the brain. Electric foot-shock exposure was chosen because of its ability to serve as fundamental and physical stress in mice. Bone marrow-derived GFP(+) cells migrated to the ventral part of the hippocampus and acquired a ramified microglia-like morphology. Microglia marker Iba1 was expressed by 100% of the ramified cells, whereas ramified cells were negative for the astrocyte marker GFAP. Compared with the case in the control group, ramified cells significantly increased after chronic exposure to stress (5 days). One month after 5 days of stress exposure, ramified cells significantly decreased in ventral hippocampus compared with the group examined immediately after the last stress exposure. We report for the first time the migration of bone marrow-derived cells to the ventral hippocampus after stress exposure. These cells have the characteristics of microglia. Mechanisms responsible for this migration and their roles in the brain remain to be determined.
Insights
Stress induces bone marrow-derived cells to migrate to the brain's hippocampus, adopting microglia characteristics. This study reveals a novel pathway for immune cell involvement in stress responses within the central nervous system.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Bone marrow-derived cells have been observed in the brain in various conditions, including neurodegeneration.
- The precise mechanisms and destinations of these migrating cells, particularly under stress, are not fully understood.
Purpose of the Study:
- To investigate the migration of bone marrow-derived cells into the brain parenchyma following stress exposure.
- To characterize the morphology and markers of these migrating cells in the hippocampus.
Main Methods:
- Bone marrow transplantation from GFP mice into recipient mice.
- Induction of stress using electric foot-shocks.
- Analysis of GFP-positive cells in the ventral hippocampus using microglia (Iba1) and astrocyte (GFAP) markers.
Main Results:
- Bone marrow-derived GFP-positive cells migrated to the ventral hippocampus after stress exposure.
- These cells acquired a ramified microglia-like morphology and expressed Iba1, but not GFAP.
- The number of these cells significantly increased after chronic stress and decreased one month post-stress.
Conclusions:
- Bone marrow-derived cells can migrate to the ventral hippocampus and exhibit microglia-like characteristics following stress.
- This finding highlights a potential role for peripheral immune cells in the brain's response to stress.
- Further research is needed to elucidate the mechanisms and functional significance of this migration.

