Early up-regulation of 18 kDa Translocator Protein in response to acute neurodegenerative damage in TREM2 deficient mice

• Published in: Neurobiology of aging 2017
• Main Authors: Belloli, Sara, Pannese, Maria, Buonsanti, Cecilia, Maiorino, Chiara, Di Grigoli, Giuseppe, Carpinelli, Assunta, Monterisi, Cristina, Moresco, Rosa Maria, Panina-Bordignon, Paola
• Format: Article
• Language: English
• Subjects: Internal Medicine; Neurology
• ISSN: 0197-4580
• DOI: 10.1016/j.neurobiolaging.2017.01.010

ABSTRACT Mutations in the TREM2 gene confer risk for Alzheimer and susceptibility for Parkinson Disease (PD). We evaluated the effect of TREM2 deletion in a MPTP-induced PD mouse model, measuring neurodegeneration and microglia activation using a combined in vivo imaging and post mortem molecular approach. In wild type (wt) mice, MPTP administration induced a progressive decrease of [11 C]FECIT uptake, culminating at day 7. Neuronal loss was accompanied by an increase of TREM2, IL-1β, and TSPO transcript levels, [11 C]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, IL-1β in response to MPTP. Likely to compensate for TREM2 absence, TREM2-/- mice showed an earlier increment of [11 C]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.