Spatio-temporal metabolic rewiring in the brain of TgF344-AD rat model of Alzheimer’s disease

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• dc.contributor.author Muñoz-Moreno, Emma
• dc.contributor.author Simões, Rui Vasco
• dc.contributor.author Tudela, Raúl
• dc.contributor.author López-Gil, Xavier
• dc.contributor.author Soria Rodríguez, Guadalupe
• dc.date.accessioned 2025-11-24T07:06:21Z
• dc.date.available 2025-11-24T07:06:21Z
• dc.date.issued 2022
• dc.description.abstract Brain damage associated with Alzheimer's disease (AD) occurs even decades before the symptomatic onset, raising the need to investigate its progression from prodromal stages. In this context, animal models that progressively display AD pathological hallmarks (e.g. TgF344-AD) become crucial. Translational technologies, such as magnetic resonance spectroscopy (MRS), enable the longitudinal metabolic characterization of this disease. However, an integrative approach is required to unravel the complex metabolic changes underlying AD progression, from early to advanced stages. TgF344-AD and wild-type (WT) rats were studied in vivo on a 7 Tesla MRI scanner, for longitudinal quantitative assessment of brain metabolic profile changes using MRS. Disease progression was investigated at 4 time points, from 9 to 18 months of age, and in 4 regions: cortex, hippocampus, striatum, and thalamus. Compared to WT, TgF344-AD rats replicated common findings in AD patients, including decreased N-acetylaspartate in the cortex, hippocampus and thalamus, and decreased glutamate in the thalamus and striatum. Different longitudinal evolution of metabolic concentration was observed between TgF344-AD and WT groups. Namely, age-dependent trajectories differed between groups for creatine in the cortex and thalamus and for taurine in cortex, with significant decreases in Tg344-AD animals; whereas myo-inositol in the thalamus and striatum showed greater increase along time in the WT group. Additional analysis revealed divergent intra- and inter-regional metabolic coupling in each group. Thus, in cortex, strong couplings of N-acetylaspartate and creatine with myo-inositol in WT, but with taurine in TgF344-AD rats were observed; whereas in the hippocampus, myo-inositol, taurine and choline compounds levels were highly correlated in WT but not in TgF344-AD animals. Furthermore, specific cortex-hippocampus-striatum metabolic crosstalks were found for taurine levels in the WT group but for myo-inositol levels in the TgF344-AD rats. With a systems biology perspective of metabolic changes in AD pathology, our results shed light into the complex spatio-temporal metabolic rewiring in this disease, reported here for the first time. Age- and tissue-dependent imbalances between myo-inositol, taurine and other metabolites, such as creatine, unveil their role in disease progression, while pointing to the inadequacy of the latter as an internal reference for quantification.en
• dc.format.mimetype application/pdf
• dc.identifier.citation Muñoz-Moreno E, Simões RV, Tudela R, López-Gil X, Soria G. Spatio-temporal metabolic rewiring in the brain of TgF344-AD rat model of Alzheimer’s disease. Sci Rep. 2022;12(1):16958. DOI: 10.1038/s41598-022-20962-6
• dc.identifier.doi http://dx.doi.org/10.1038/s41598-022-20962-6
• dc.identifier.issn 2045-2322
• dc.identifier.uri http://hdl.handle.net/10230/71976
• dc.language.iso eng
• dc.publisher Nature Research
• dc.relation.ispartof Scientific Reports. 2022;12(1):16958
• dc.rights This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.other Alzheimer, Malaltia d'ca
• dc.subject.other Espectroscopisca
• dc.subject.other Ressonància magnèticaca
• dc.title Spatio-temporal metabolic rewiring in the brain of TgF344-AD rat model of Alzheimer’s diseaseen
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion