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TREM2 deficiency impairs chemotaxis and microglial responses to neuronal injury

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TREM2 deficiency impairs chemotaxis and microglial responses to neuronal injury. / Mazaheri, Fargol; Snaidero, Nicolas; Kleinberger, Gernot; Madore, Charlotte; Daria, Anna; Werner, Georg; Krasemann, Susanne; Capell, Anja; Trümbach, Dietrich; Wurst, Wolfgang; Brunner, Bettina; Bultmann, Sebastian; Tahirovic, Sabina; Kerschensteiner, Martin; Misgeld, Thomas; Butovsky, Oleg; Haass, Christian.

in: EMBO REP, Jahrgang 18, Nr. 7, 07.2017, S. 1186-1198.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Mazaheri, F, Snaidero, N, Kleinberger, G, Madore, C, Daria, A, Werner, G, Krasemann, S, Capell, A, Trümbach, D, Wurst, W, Brunner, B, Bultmann, S, Tahirovic, S, Kerschensteiner, M, Misgeld, T, Butovsky, O & Haass, C 2017, 'TREM2 deficiency impairs chemotaxis and microglial responses to neuronal injury', EMBO REP, Jg. 18, Nr. 7, S. 1186-1198. https://doi.org/10.15252/embr.201743922

APA

Mazaheri, F., Snaidero, N., Kleinberger, G., Madore, C., Daria, A., Werner, G., Krasemann, S., Capell, A., Trümbach, D., Wurst, W., Brunner, B., Bultmann, S., Tahirovic, S., Kerschensteiner, M., Misgeld, T., Butovsky, O., & Haass, C. (2017). TREM2 deficiency impairs chemotaxis and microglial responses to neuronal injury. EMBO REP, 18(7), 1186-1198. https://doi.org/10.15252/embr.201743922

Vancouver

Mazaheri F, Snaidero N, Kleinberger G, Madore C, Daria A, Werner G et al. TREM2 deficiency impairs chemotaxis and microglial responses to neuronal injury. EMBO REP. 2017 Jul;18(7):1186-1198. https://doi.org/10.15252/embr.201743922

Bibtex

@article{65b50af98a824ae8b7abd96c0781685d,
title = "TREM2 deficiency impairs chemotaxis and microglial responses to neuronal injury",
abstract = "Sequence variations in the triggering receptor expressed on myeloid cells 2 (TREM2) have been linked to an increased risk for neurodegenerative disorders such as Alzheimer's disease and frontotemporal lobar degeneration. In the brain, TREM2 is predominantly expressed in microglia. Several disease-associated TREM2 variants result in a loss of function by reducing microglial phagocytosis, impairing lipid sensing, preventing binding of lipoproteins and affecting shielding of amyloid plaques. We here investigate the consequences of TREM2 loss of function on the microglia transcriptome. Among the differentially expressed messenger RNAs in wild-type and Trem2(-/-) microglia, gene clusters are identified which represent gene functions in chemotaxis, migration and mobility. Functional analyses confirm that loss of TREM2 impairs appropriate microglial responses to injury and signals that normally evoke chemotaxis on multiple levels. In an ex vivo organotypic brain slice assay, absence of TREM2 reduces the distance migrated by microglia. Moreover, migration towards defined chemo-attractants is reduced upon ablation of TREM2 and can be rescued by TREM2 re-expression. In vivo, microglia lacking TREM2 migrate less towards injected apoptotic neurons, and outgrowth of microglial processes towards sites of laser-induced focal CNS damage in the somatosensory cortex is slowed. The apparent lack of chemotactic stimulation upon depletion of TREM2 is consistent with a stable expression profile of genes characterizing the homoeostatic signature of microglia.",
keywords = "Journal Article",
author = "Fargol Mazaheri and Nicolas Snaidero and Gernot Kleinberger and Charlotte Madore and Anna Daria and Georg Werner and Susanne Krasemann and Anja Capell and Dietrich Tr{\"u}mbach and Wolfgang Wurst and Bettina Brunner and Sebastian Bultmann and Sabina Tahirovic and Martin Kerschensteiner and Thomas Misgeld and Oleg Butovsky and Christian Haass",
note = "{\textcopyright} 2017 The Authors.",
year = "2017",
month = jul,
doi = "10.15252/embr.201743922",
language = "English",
volume = "18",
pages = "1186--1198",
journal = "EMBO REP",
issn = "1469-221X",
publisher = "NATURE PUBLISHING GROUP",
number = "7",

}

RIS

TY - JOUR

T1 - TREM2 deficiency impairs chemotaxis and microglial responses to neuronal injury

AU - Mazaheri, Fargol

AU - Snaidero, Nicolas

AU - Kleinberger, Gernot

AU - Madore, Charlotte

AU - Daria, Anna

AU - Werner, Georg

AU - Krasemann, Susanne

AU - Capell, Anja

AU - Trümbach, Dietrich

AU - Wurst, Wolfgang

AU - Brunner, Bettina

AU - Bultmann, Sebastian

AU - Tahirovic, Sabina

AU - Kerschensteiner, Martin

AU - Misgeld, Thomas

AU - Butovsky, Oleg

AU - Haass, Christian

N1 - © 2017 The Authors.

PY - 2017/7

Y1 - 2017/7

N2 - Sequence variations in the triggering receptor expressed on myeloid cells 2 (TREM2) have been linked to an increased risk for neurodegenerative disorders such as Alzheimer's disease and frontotemporal lobar degeneration. In the brain, TREM2 is predominantly expressed in microglia. Several disease-associated TREM2 variants result in a loss of function by reducing microglial phagocytosis, impairing lipid sensing, preventing binding of lipoproteins and affecting shielding of amyloid plaques. We here investigate the consequences of TREM2 loss of function on the microglia transcriptome. Among the differentially expressed messenger RNAs in wild-type and Trem2(-/-) microglia, gene clusters are identified which represent gene functions in chemotaxis, migration and mobility. Functional analyses confirm that loss of TREM2 impairs appropriate microglial responses to injury and signals that normally evoke chemotaxis on multiple levels. In an ex vivo organotypic brain slice assay, absence of TREM2 reduces the distance migrated by microglia. Moreover, migration towards defined chemo-attractants is reduced upon ablation of TREM2 and can be rescued by TREM2 re-expression. In vivo, microglia lacking TREM2 migrate less towards injected apoptotic neurons, and outgrowth of microglial processes towards sites of laser-induced focal CNS damage in the somatosensory cortex is slowed. The apparent lack of chemotactic stimulation upon depletion of TREM2 is consistent with a stable expression profile of genes characterizing the homoeostatic signature of microglia.

AB - Sequence variations in the triggering receptor expressed on myeloid cells 2 (TREM2) have been linked to an increased risk for neurodegenerative disorders such as Alzheimer's disease and frontotemporal lobar degeneration. In the brain, TREM2 is predominantly expressed in microglia. Several disease-associated TREM2 variants result in a loss of function by reducing microglial phagocytosis, impairing lipid sensing, preventing binding of lipoproteins and affecting shielding of amyloid plaques. We here investigate the consequences of TREM2 loss of function on the microglia transcriptome. Among the differentially expressed messenger RNAs in wild-type and Trem2(-/-) microglia, gene clusters are identified which represent gene functions in chemotaxis, migration and mobility. Functional analyses confirm that loss of TREM2 impairs appropriate microglial responses to injury and signals that normally evoke chemotaxis on multiple levels. In an ex vivo organotypic brain slice assay, absence of TREM2 reduces the distance migrated by microglia. Moreover, migration towards defined chemo-attractants is reduced upon ablation of TREM2 and can be rescued by TREM2 re-expression. In vivo, microglia lacking TREM2 migrate less towards injected apoptotic neurons, and outgrowth of microglial processes towards sites of laser-induced focal CNS damage in the somatosensory cortex is slowed. The apparent lack of chemotactic stimulation upon depletion of TREM2 is consistent with a stable expression profile of genes characterizing the homoeostatic signature of microglia.

KW - Journal Article

U2 - 10.15252/embr.201743922

DO - 10.15252/embr.201743922

M3 - SCORING: Journal article

C2 - 28483841

VL - 18

SP - 1186

EP - 1198

JO - EMBO REP

JF - EMBO REP

SN - 1469-221X

IS - 7

ER -