کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
4932618 | 1433531 | 2017 | 36 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Early upregulation of 18-kDa translocator protein in response to acute neurodegenerative damage in TREM2-deficient mice
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
سالمندی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
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 (TREM2â/â) 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, TREM2â/â 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.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neurobiology of Aging - Volume 53, May 2017, Pages 159-168
Journal: Neurobiology of Aging - Volume 53, May 2017, Pages 159-168
نویسندگان
Sara Belloli, Maria Pannese, Cecilia Buonsanti, Chiara Maiorino, Giuseppe Di Grigoli, Assunta Carpinelli, Cristina Monterisi, Rosa Maria Moresco, Paola Panina-Bordignon,