Early upregulation of 18-kDa translocator protein in response to acute neurodegenerative damage in TREM2-deficient mice

Sara Belloli, M Pannese, C Buonsanti, C Maiorino, G Di Grigoli, A Carpinelli, C Monterisi, RM Moresco, P Panina-Bordignon

Research output: Contribution to journalArticle

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Abstract

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 [11C]FECIT uptake, culminating at day 7. Neuronal loss was accompanied by an increase of TREM2, IL-1β, and translocator protein (TSPO) transcript levels, [11C]PK11195 binding and GFAP staining (from day 2), and an early and transient increase of TNF-α, 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-α, and IL-1β in response to MPTP. Likely to compensate for TREM2 absence, TREM2−/− mice showed an earlier increment of [11C]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. © 2017 Elsevier Inc.
Original languageEnglish
Pages (from-to)159-168
Number of pages10
JournalNeurobiology of Aging
Volume53
Issue number8
DOIs
Publication statusPublished - 2017

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1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
Up-Regulation
Microglia
Interleukin-1
Parkinson Disease
Proteins
Staining and Labeling
Galectin 3
Molecular Imaging
Disease Susceptibility
Interleukin-4
Immune System
Cell Survival
Alzheimer Disease
Neurons
Mutation
Genes
(R)-(11C)1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinolinecarboxamide

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Early upregulation of 18-kDa translocator protein in response to acute neurodegenerative damage in TREM2-deficient mice. / Belloli, Sara; Pannese, M; Buonsanti, C; Maiorino, C; Di Grigoli, G; Carpinelli, A; Monterisi, C; Moresco, RM; Panina-Bordignon, P.

In: Neurobiology of Aging, Vol. 53, No. 8, 2017, p. 159-168.

Research output: Contribution to journalArticle

Belloli, S, Pannese, M, Buonsanti, C, Maiorino, C, Di Grigoli, G, Carpinelli, A, Monterisi, C, Moresco, RM & Panina-Bordignon, P 2017, 'Early upregulation of 18-kDa translocator protein in response to acute neurodegenerative damage in TREM2-deficient mice', Neurobiology of Aging, vol. 53, no. 8, pp. 159-168. https://doi.org/10.1016/j.neurobiolaging.2017.01.010
Belloli, Sara ; Pannese, M ; Buonsanti, C ; Maiorino, C ; Di Grigoli, G ; Carpinelli, A ; Monterisi, C ; Moresco, RM ; Panina-Bordignon, P. / Early upregulation of 18-kDa translocator protein in response to acute neurodegenerative damage in TREM2-deficient mice. In: Neurobiology of Aging. 2017 ; Vol. 53, No. 8. pp. 159-168.
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