3.6 Effects of LSL60101 on microglia activation and inflammatory markers expression.
In the AD brain, the formation of Aβ plaques leads to the activation of astrocytes and reactive gliosis. To examine changes in microglia reactivity, Iba-1 was determined by IHC experiments. Importantly, LSL60101 treatment resulted in a significant decrease in Iba-1 levels in the hippocampus of 5XFAD mice whereas donepezil did not affect Iba-1 immunoreactivity (Figure 5a-5d). Donepezil/LSL60101 combination did not modify the beneficial effect of LSL60101 by itself on microglia activation.
The gene expression of different inflammatory mediators was evaluated in the hippocampus of 5XFAD mice. In whole, 5XFAD mice presented an evident exacerbation of inflammatory response compared to WT mice, whereas treatments led to the upregulation of specific markers studied. Interestingly, significant increases or tendency to increase were determined inInterleukin 1β (Il-1b),Interleukin 6 (Il-6), andChemokine (C-C motif) ligand 12 (Ccl12) markers in LSL60101 treated group, while donepezil alone had no significant effect on these markers (Figure 5e). Moreover, the gene expression of Triggering receptor expressed on myeloid cells 2 (Trem2 ) was increased significantly after treatment with the I2-IR ligand LSL60101 (Figure 5f).