Early upregulation of 18-kDa translocator protein in response to acute neurodegenerative damage in TREM2-deficient mice
| Autor: | Sara Belloli a, b, c, Maria Pannese d, Cecilia Buonsanti e, Chiara Maiorino e, Giuseppe Di Grigoli a, Assunta Carpinelli a, Cristina Monterisi f, Rosa Maria Moresco b, f, Paola Panina-Bordignon d. |
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| Přispěvatelé: | Belloli, S., Pannese, M., Buonsanti, C., Maiorino, C., Di Grigoli, G., Carpinelli, A., Monterisi, C., Moresco, R. M., Panina-Bordignon, P., Belloli, S, Pannese, M, Buonsanti, C, Maiorino, C, Di Grigoli, G, Carpinelli, A, Monterisi, C, Moresco, R, Panina Bordignon, P |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Aging Interleukin-1beta 18-kDa translocator protein Triggering receptor expressed on myeloid cells 2 chemistry.chemical_compound 0302 clinical medicine Neuroinflammation Receptors Immunologic Membrane Glycoproteins Microglia biology General Neuroscience MPTP Neurodegeneration Up-Regulation Parkinson disease medicine.anatomical_structure 1-Methyl-4-phenyl-1 2 3 6-tetrahydropyridine Acute Disease Positron emission tomography medicine.medical_specialty Mice Transgenic 03 medical and health sciences Downregulation and upregulation Internal medicine medicine Translocator protein Animals Parkinson Disease Secondary Neuroscience (all) TREM2 Receptors GABA-A medicine.disease Mice Inbred C57BL Disease Models Animal 030104 developmental biology Endocrinology chemistry Nerve Degeneration Immunology biology.protein Neurology (clinical) Neuron Geriatrics and Gerontology Carrier Proteins Gene Deletion 030217 neurology & neurosurgery Developmental Biology |
| Zdroj: | Neurobiology of aging (Online) 53 (2017): 159–168. doi:10.1016/j.neurobiolaging.2017.01.010 info:cnr-pdr/source/autori:Sara Belloli a,b,c, Maria Pannese d, Cecilia Buonsanti e, Chiara Maiorino e, Giuseppe Di Grigoli a,b, Assunta Carpinelli a, Cristina Monterisi f, Rosa Maria Moresco b,c,f, Paola Panina-Bordignon d./titolo:Early upregulation of 18-kDa translocator protein in response to acute neurodegenerative damage in TREM2-deficient mice/doi:10.1016%2Fj.neurobiolaging.2017.01.010/rivista:Neurobiology of aging (Online)/anno:2017/pagina_da:159/pagina_a:168/intervallo_pagine:159–168/volume:53 |
| DOI: | 10.1016/j.neurobiolaging.2017.01.010 |
| Popis: | 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 invivo 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. |
| Databáze: | OpenAIRE |
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