Microglial TREM2 promotes phagocytic clearance of damaged neurons after status epilepticus.

Autor: Bosco DB; Department of Neurology, Mayo Clinic, Rochester, MN, USA., Kremen V; Department of Neurology, Mayo Clinic, Rochester, MN, USA., Haruwaka K; Center for Neuroimmunology and Glial Biology, Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX, USA., Zhao S; Department of Neurology, Mayo Clinic, Rochester, MN, USA; Center for Neuroimmunology and Glial Biology, Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX, USA., Wang L; Department of Neurology, Mayo Clinic, Rochester, MN, USA., Ebner BA; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA., Zheng J; Center for Neuroimmunology and Glial Biology, Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX, USA., Xie M; Department of Neurology, Mayo Clinic, Rochester, MN, USA., Dheer A; Department of Neurology, Mayo Clinic, Rochester, MN, USA., Perry JF; Department of Neurology, Mayo Clinic, Rochester, MN, USA., Barath A; Department of Neurology, Mayo Clinic, Rochester, MN, USA; Center for Neuroimmunology and Glial Biology, Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX, USA., Nguyen AT; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA., Worrell GA; Department of Neurology, Mayo Clinic, Rochester, MN, USA., Wu LJ; Department of Neurology, Mayo Clinic, Rochester, MN, USA; Center for Neuroimmunology and Glial Biology, Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX, USA. Electronic address: longjun.wu@uth.tmc.edu.
Jazyk: angličtina
Zdroj: Brain, behavior, and immunity [Brain Behav Immun] 2025 Jan; Vol. 123, pp. 540-555. Date of Electronic Publication: 2024 Sep 29.
DOI: 10.1016/j.bbi.2024.09.034
Abstrakt: 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.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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