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2022-10-25

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cc-by (c) Companys Alemany, Júlia et al., 2022
Please use this identifier to cite or link to this item: https://hdl.handle.net/2445/194102

Glial cell reactivity and oxidative stress prevention in Alzheimer's disease mice model by an optimized NMDA receptor antagonist

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https://doi.org/10.1038/s41598-022-22963-x

Abstract

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 reactivity as revealed by glial fibrillary acidic protein (GFAP) and ionized calcium-binding adapter molecule 1 (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 cytokines Il-1β, Ifn-γ, Ccl2 and Ccl3 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. Hence, our results reveal a robust effect on neuroinflammation and OS processes after UB-ALT-EV treatment, surpassing the memantine effect in 5XFAD.

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Envelliment, Malaltia d'Alzheimer, Receptors cel·lulars

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Aging, Alzheimer's disease, Cell receptors

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Articles publicats en revistes (Farmacologia, Toxicologia i Química Terapèutica)

Citation

COMPANYS ALEMANY, Júlia, et al. Glial cell reactivity and oxidative stress prevention in Alzheimer's disease mice model by an optimized NMDA receptor antagonist. Scientific Reports. 2022. Vol. 12, num. 17908. ISSN 2045-2322. [consulted: 10 of August of 2026]. Available at: https://hdl.handle.net/2445/194102

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