Journal
NEUROBIOLOGY OF AGING
Volume 53, Issue -, Pages 159-168Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.neurobiolaging.2017.01.010
Keywords
Triggering receptor expressed on myeloid cells 2; Parkinson disease; Neuroinflammation; 18-kDa translocator protein; Positron emission tomography
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Funding
- European Union's Seventh Framework Programme (FP7) [278850]
- Framework Agreement Lombardy Region - National Research Council of Italy
- Italian Ministry of Education, University and Research (MIUR) [CTN01 00177 165430]
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Mutations in the TREM2 gene confer risk for Alzheimer's disease and susceptibility for Parkinson's disease (PD). We evaluated the effect of TREM2 deletion in a 1-methyl 4-phenyl 1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model, measuring neurodegeneration and microglia activation using a combined in vivo imaging and postmortem molecular approach. In wild-type mice, MPTP administration induced a progressive decrease of [C-11] FECIT uptake, culminating at day 7. Neuronal loss was accompanied by an increase of TREM2, IL-1 beta, and translocator protein (TSPO) transcript levels, [C-11]PK11195 binding and GFAP staining (from day 2), and an early and transient increase of TNF-alpha, Galectin-3, and Iba-1 (from day 1). In TREM2 null (TREM2(-/-)) mice, MPTP similarly affected neuron viability and microglial cells, as shown by the lower level of Iba-1 staining in basal condition, and reduced increment of Iba-1, TNF-alpha, and IL-1 beta in response to MPTP. Likely to compensate for TREM2 absence, TREM2(-/-) mice showed an earlier increment of [C-11] PK11195 binding and a significant increase of IL-4. Taken together, our data demonstrate a central role of TREM2 in the regulation of microglia response to acute neurotoxic insults and suggest a potential modulatory role of TSPO in response to immune system deficit. (C) 2017 Elsevier Inc. All rights reserved.
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