Abstract
| Original language | English |
|---|---|
| Pages (from-to) | 159-168 |
| Number of pages | 10 |
| Journal | Neurobiology of Aging |
| Volume | 53 |
| Issue number | 8 |
| DOIs | |
| Publication status | Published - 2017 |
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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 journal › Article
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TY - JOUR
T1 - Early upregulation of 18-kDa translocator protein in response to acute neurodegenerative damage in TREM2-deficient mice
AU - Belloli, Sara
AU - Pannese, M
AU - Buonsanti, C
AU - Maiorino, C
AU - Di Grigoli, G
AU - Carpinelli, A
AU - Monterisi, C
AU - Moresco, RM
AU - Panina-Bordignon, P
PY - 2017
Y1 - 2017
N2 - 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.
AB - 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.
U2 - 10.1016/j.neurobiolaging.2017.01.010
DO - 10.1016/j.neurobiolaging.2017.01.010
M3 - Article
VL - 53
SP - 159
EP - 168
JO - Neurobiology of Aging
JF - Neurobiology of Aging
SN - 0197-4580
IS - 8
ER -