title: Early upregulation of 18-kDa translocator protein in response to acute neurodegenerative damage in TREM2-deficient mice.
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.
authors.affiliation: Institute of Bioimages and Molecular Physiology, National Research Council, Segrate, MI, Italy; Milan Center for Neuroscience (NeuroMi), Milan, Italy; Experimental Imaging Center, IRCCS San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Belloli
authors.affiliation: Division of Genetics and Cell Biology, IRCCS San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Pannese
authors.affiliation: Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Buonsanti
authors.affiliation: Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Maiorino
authors.affiliation: Institute of Bioimages and Molecular Physiology, National Research Council, Segrate, MI, Italy; Milan Center for Neuroscience (NeuroMi), Milan, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Di Grigoli
authors.affiliation: Institute of Bioimages and Molecular Physiology, National Research Council, Segrate, MI, Italy.
authors.forename: Assunta
authors.initials: A
authors.lastname: Carpinelli
authors.affiliation: Department of Medicine and Surgery, University of Milan Bicocca, Monza, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Monterisi
authors.affiliation: Milan Center for Neuroscience (NeuroMi), Milan, Italy; Experimental Imaging Center, IRCCS San Raffaele Scientific Institute, Milan, Italy; Department of Medicine and Surgery, University of Milan Bicocca, Monza, Italy. Electronic address: moresco.rosamaria@hsr.it.
authors.forename: Rosa Maria
authors.initials: RM
authors.lastname: Moresco
authors.affiliation: Division of Genetics and Cell Biology, IRCCS San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Panina-Bordignon
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000208:Acute Disease; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism*; D004195:Disease Models, Animal; D017353:Gene Deletion; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000172:deficiency* / Q000235:genetics*; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017628:Microglia / Q000473:pathology; D009410:Nerve Degeneration / Q000235:genetics* / Q000473:pathology; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000235:genetics* / Q000276:immunology / Q000473:pathology*; D011963:Receptors, GABA-A / Q000235:genetics* / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000172:deficiency* / Q000235:genetics*; D015854:Up-Regulation
chemical_list: D002352:Carrier Proteins; D053583:Interleukin-1beta; D008562:Membrane Glycoproteins; D011963:Receptors, GABA-A; D011971:Receptors, Immunologic; C498716:Trem2 protein, mouse; C069997:Tspo protein, rat; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
keywords: 18-kDa translocator protein; Neuroinflammation; Parkinson disease; Positron emission tomography; Triggering receptor expressed on myeloid cells 2