Related Experiment Video
Updated: Aug 20, 2025
Investigations on Alterations of Hippocampal Circuit Function Following Mild Traumatic Brain Injury
Published on: November 19, 2012
Preliminary analysis of hippocampus synaptic apoptosis and microglial phagocytosis induced by severe restraint stress
Shingo Enomoto1,2, Masahiro Ohgidani2,3, Noriaki Sagata2
1Self Defense Force, Fukuoka Hospital, Fukuoka, Japan.
Aim:
Several studies reported stress-induced microglial phagocytosis, but the biochemical mechanisms by which stress alters microglial synaptic phagocytosis are not fully uncovered. Local or limited apoptosis without cell death was observed at neuronal synapses in previous studies, and proposed as an upstream mechanism for microglial synapse elimination. In this micro-report, we aimed to preliminary examine local synaptic apoptosis in the mouse hippocampus following severe restraint stress, and its effect on microglial phagocytosis.
Methods:
Mice were exposed to 10-day water immersion restraint stress (WIRS). Brain sections including stratum lucidum in the hippocampal CA3 subfield were stained with antibodies against cleaved caspase 3, ionized calcium-binding adapter molecule1 (Iba1), lysosomal-associated membrane protein1 (LAMP1), vesicular glutamate transporter1 (VGLUT1). Co-localization among these proteins were calculated.
Results:
Our image analysis revealed that synaptic apoptosis was increased while there were no significant changes in microglial phagocytic activity and synaptic phagocytosis following 10-day WIRS.
Conclusion:
Severe restraint stress enhanced pre-synaptic apoptosis in mouse CA3 stratum lucidum region, but did not promote microglial phagocytosis. The phenomenon microglia fail to phagocytose weakened and unnecessary synapses may be related to pathology of stress.
Insights
Severe restraint stress increased synaptic apoptosis in mice but did not affect microglial phagocytosis. This suggests a failure in microglia
Area of Science:
- Neuroscience
- Cell Biology
- Stress Research
Background:
- Stress impacts microglial function, but mechanisms altering synaptic phagocytosis are unclear.
- Synaptic apoptosis without cell death is a proposed upstream event for microglial synapse elimination.
Purpose of the Study:
- To investigate synaptic apoptosis in the mouse hippocampus after restraint stress.
- To determine the effect of stress-induced synaptic apoptosis on microglial phagocytosis.
Main Methods:
- Mice underwent 10-day water immersion restraint stress (WIRS).
- Hippocampal sections were stained for cleaved caspase 3, Iba1, LAMP1, and VGLUT1.
- Co-localization analysis quantified synaptic apoptosis and microglial phagocytosis.
Main Results:
- Synaptic apoptosis significantly increased in the CA3 stratum lucidum after 10-day WIRS.
- No significant changes were observed in overall microglial phagocytic activity or synaptic phagocytosis.
Conclusions:
- Severe restraint stress enhances pre-synaptic apoptosis in the hippocampus.
- Microglial phagocytosis of weakened synapses is impaired under stress conditions, potentially contributing to stress-related pathology.
