Language

English

Publication Date

1-1-2025

Journal

Brain, Behavior, and Immunity

DOI

10.1016/j.bbi.2024.09.034

PMID

39353548

PMCID

PMC11924143

PubMedCentral® Posted Date

1-1-2026

PubMedCentral® Full Text Version

Author MSS

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.

Keywords

Receptors, Immunologic, Animals, Status Epilepticus, Microglia, Membrane Glycoproteins, Mice, Knockout, Male, Phagocytosis, Mice, Neurons, Humans, Disease Models, Animal, Kainic Acid, Mice, Inbred C57BL, Epilepsy, Temporal Lobe, Seizures, Antigens, CD, Antigens, Differentiation, Myelomonocytic, Microglia, Seizures, Epilepsy, TREM2, Phagocytosis, CD68

Published Open-Access

yes

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