Related Experiment Video
Updated: Aug 6, 2026
Assessing Retinal Microglial Phagocytic Function In Vivo Using a Flow Cytometry-based Assay
Published on: October 18, 2016
Microglial TREM2 promotes phagocytic clearance of damaged neurons after status epilepticus
Dale B Bosco1, Vaclav Kremen1, Koichiro Haruwaka2
1Department of Neurology, Mayo Clinic, Rochester, MN, USA.
Abstract:
In the central nervous system, triggering receptor expressed on myeloid cells 2 (TREM2) is exclusively expressed by microglia and is critical for microglial proliferation, migration, and phagocytosis. Microglial TREM2 plays an important role in neurodegenerative diseases, such as Alzheimer's disease and amyotrophic lateral sclerosis. However, little is known about how TREM2 affects microglial function within epileptogenesis. To investigate this, we utilized male TREM2 knockout (KO) mice within the intra-amygdala kainic acid seizure model. Electroencephalographic analysis, immunocytochemistry, and RNA sequencing revealed that TREM2 deficiency significantly promoted seizure-induced pathology. We found that TREM2 KO increased both the severity of acute status epilepticus and the number of spontaneous recurrent seizures characteristic of chronic focal epilepsy. Phagocytic clearance of damaged neurons by microglia was also impaired by TREM2 KO and reduced phagocytic activity correlated with increased spontaneous seizures. Analysis of human tissue from patients who underwent surgical resection for drug resistant temporal lobe epilepsy also showed a negative correlation between expression of the microglial phagocytic marker CD68 and focal to bilateral tonic-clonic generalized seizure history. These results indicate that microglial TREM2 and phagocytic activity are important to epileptogenic pathology.
Insights
Triggering receptor expressed on myeloid cells 2 (TREM2) deficiency worsens epilepsy by impairing microglial function. Reduced TREM2 and microglial phagocytosis correlate with increased seizure severity and frequency in mice and humans.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Triggering receptor expressed on myeloid cells 2 (TREM2) is crucial for microglial functions like proliferation, migration, and phagocytosis in the central nervous system.
- Microglial TREM2 is implicated in neurodegenerative diseases, but its role in epileptogenesis remains unclear.
Purpose of the Study:
- To investigate the impact of TREM2 deficiency on microglial function and seizure pathology in the context of epileptogenesis.
- To explore the correlation between microglial phagocytic activity and seizure history in epilepsy patients.
Main Methods:
- Utilized male TREM2 knockout (KO) mice in an intra-amygdala kainic acid seizure model.
- Performed electroencephalographic analysis, immunocytochemistry, and RNA sequencing.
- Analyzed human temporal lobe epilepsy patient tissue for correlations between CD68 expression and seizure history.
Main Results:
- TREM2 deficiency significantly exacerbated seizure-induced pathology, increasing acute status epilepticus severity and spontaneous recurrent seizures.
- Impaired microglial phagocytic clearance of damaged neurons was observed in TREM2 KO mice.
- Reduced CD68 expression (a microglial phagocytic marker) in human epilepsy patients correlated negatively with a history of focal to bilateral tonic-clonic generalized seizures.
Conclusions:
- Microglial TREM2 plays a critical role in mitigating seizure-induced pathology.
- Impaired microglial phagocytosis due to TREM2 deficiency contributes to epileptogenesis.
- TREM2-mediated microglial function is a potential therapeutic target for epilepsy.
