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Merck

TREM2 regulates microglial cell activation in response to demyelination in vivo.

Acta neuropathologica (2015-01-30)
Claudia Cantoni, Bryan Bollman, Danilo Licastro, Mingqiang Xie, Robert Mikesell, Robert Schmidt, Carla M Yuede, Daniela Galimberti, Gunilla Olivecrona, Robyn S Klein, Anne H Cross, Karel Otero, Laura Piccio
ABSTRACT

Microglia are phagocytic cells that survey the brain and perform neuroprotective functions in response to tissue damage, but their activating receptors are largely unknown. Triggering receptor expressed on myeloid cells 2 (TREM2) is a microglial immunoreceptor whose loss-of-function mutations in humans cause presenile dementia, while genetic variants are associated with increased risk of neurodegenerative diseases. In myeloid cells, TREM2 has been involved in the regulation of phagocytosis, cell proliferation and inflammatory responses in vitro. However, it is unknown how TREM2 contributes to microglia function in vivo. Here, we identify a critical role for TREM2 in the activation and function of microglia during cuprizone (CPZ)-induced demyelination. TREM2-deficient (TREM2(-/-)) mice had defective clearance of myelin debris and more axonal pathology, resulting in impaired clinical performances compared to wild-type (WT) mice. TREM2(-/-) microglia proliferated less in areas of demyelination and were less activated, displaying a more resting morphology and decreased expression of the activation markers MHC II and inducible nitric oxide synthase as compared to WT. Mechanistically, gene expression and ultrastructural analysis of microglia suggested a defect in myelin degradation and phagosome processing during CPZ intoxication in TREM2(-/-) microglia. These findings place TREM2 as a key regulator of microglia activation in vivo in response to tissue damage.

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Sigma-Aldrich
Chlorpromazine hydrochloride, ≥98% (TLC)
Sigma-Aldrich
Bis(cyclohexanone)oxaldihydrazone, ≥95% (TLC)
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Anticorpo anti-proteina basica della mielina, serum, Chemicon®
Supelco
Bis(cyclohexanone)oxaldihydrazone, for spectrophotometric det. of Cu, ≥99.0%
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Chlorpromazine hydrochloride, meets USP testing specifications
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Chlorpromazine hydrochloride, VETRANAL®, analytical standard
USP
Chlorpromazine hydrochloride, United States Pharmacopeia (USP) Reference Standard
Chlorpromazine hydrochloride, European Pharmacopoeia (EP) Reference Standard