Early up-regulation 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 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.