Project description:In Alzheimer's disease pathology, several neuronal processes are dysregulated by excitotoxicity including neuroinflammation and oxidative stress (OS). New therapeutic agents capable of modulating such processes are needed to foster neuroprotection. Here, the effect of an optimised NMDA receptor antagonist, UB-ALT-EV and memantine, as a gold standard, have been evaluated in 5XFAD mice. Following treatment with UB-ALT-EV, nor memantine, changes in the calcineurin (CaN)/NFAT pathway were detected. UB-ALT-EV increased neurotropic factors (Bdnf, Vgf and Ngf) gene expression. Treatments reduced astrocytic and microglial activation as revealed by GFAP and Iba-1 quantification. Interestingly, only UB-ALT-EV was able to reduce gene expression of Trem2, a marker of microglial activation and NF-κB. Pro-inflammatory M1-microglial phenotype (Il-1β, Ifn-γ, Ccl2 and Ccl3) markers were down-regulated in UB-ALT-EV-treated mice but not in memantine-treated mice. Interestingly, the anti-inflammatory markers of the M2-migroglial phenotype, chitinase-like 3 (Ym1) and Arginase-1 (Arg1), were up-regulated after treatment with UB-ALT-EV. Since iNOS gene expression decreased after UB-ALT-EV treatment, a qPCR array containing 84 OS-related genes was performed. We found changes in Il-19, Il-22, Gpx6, Ncf1, Aox1 and Vim gene expression after UB-ALT-EV. In sum, our results reveal a robust effect on neuroinflammation and OS processes after UB-ALT-EV treatment, surpassing the memantine effect in 5XFAD.
Project description:Transcriptome analysis of hippocampal RNA samples from wild-type, 5xFAD, 5xFAD;eIF2α+/S51A and eIF2α+/S51A mice Our transcriptome analyses showed clear transcriptional alterations in hippocampi of 5xFAD compared to wild type mice that were not corrected by the eIF2αS51A allele. Hemizygous 5xFAD mice, which were on a genetic background of B6/SJL, were crossed with eIF2α+/S51A mice (C57BL/6J background), to generate the offspring that was analyzed in the microarray. Hippocampal samples of 12 mice (4 groups: wild-type, 5xFAD, 5xFAD;eIF2α+/S51A and eIF2α+/S51A) were processed using Affymetrix Mouse Exon 1.0 ST platform. Array data was processed by Affymetrix Exon Array Computational Tool. No technical replicates were performed.
Project description:Analysis of steady-state mRNA levels in mouse brain hippocampus tissue at 9 months from wild-type C57BL/6J, Dp16, 5xFAD, and 5xFAD-Dp16 mice.
Project description:Analysis of steady-state mRNA levels in mouse brain cortex tissue at 9 months from wild-type C57BL/6J, Dp16, 5xFAD, and 5xFAD-Dp16 mice.
Project description:Analysis of steady-state mRNA levels in mouse brain hippocampus tissue at 5 months from wild-type C57BL/6J, Dp16, 5xFAD, and 5xFAD-Dp16 mice.
Project description:Analysis of steady-state mRNA levels in mouse brain cortex tissue at 5 months from wild-type C57BL/6J, Dp16, 5xFAD, and 5xFAD-Dp16 mice.
Project description:Analysis of steady-state mRNA levels in mouse brain hippocampus tissue at 9 months from wild-type C57BL/6J, Dp16, 5xFAD, and 5xFAD-Dp16 mice.
Project description:Spatial transcriptomics analysis was performed to detect differential gene expression in brain sections of of wild type, 5XFAD mice (model of Alzheimer's Disease), 5XFAD mice treated with either vehicle or human neural stem cells (hNSC)
Project description:Analysis of steady-state mRNA levels in mouse brain hippocampus tissue at 5 months from wild-type C57BL/6J, Dp16, 5xFAD, and 5xFAD-Dp16 mice.