Dataset Information

Comprehensive evaluation of Ubiquinol-supplemented diet effects in the 3xTg AD mice using MALDI-MSI

ABSTRACT: Alzheimer's disease (AD) is a chronic neurodegenerative disorder, accounting for up to 75 % of all dementia cases. Although the basis of AD etiology remains unknown, oxidative stress constitutes a major driver given its intimate association, specially at prodromic stages of the disease. In this line, Ubiquinol, the reduced form of coenzyme Q10, is a well-known neuroprotective antioxidant and has demonstrated significant effects in oxidative responses of β-Amyloid aggregation, internalization, and apoptosis-induced neurodegeneration. However, full extent of Ubiquinol effects in the context of AD is not yet known in detail. In this study, we designed a new methodology based on MALDI MSI for evaluating the peptide profile of the 3xTg-AD mice model fed a Ubiquinol-supplemented diet. By adopting functional analysis tools, we observed differential functional profile in hippocampus and cortex levels after 4- or 10-m o supplementation. Therefore, we also identified ACAD9, XPO1 and EIF3A as potential protein references for the diagnosis of AD at early/late stages.

INSTRUMENT(S): TripleTOF 5600

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Brain

SUBMITTER: Emilio Llanos González

LAB HEAD: Mario Durán Prado

PROVIDER: PXD037763 | Pride | 2023-05-10

REPOSITORIES: Pride

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Publications

Spatial and Temporal Protein Modules Signatures Associated with Alzheimer Disease in 3xTg-AD Mice Are Restored by Early Ubiquinol Supplementation.

Llanos-González Emilio E Sancho-Bielsa Francisco J FJ Frontiñán-Rubio Javier J Rabanal-Ruíz Yoana Y García-Carpintero Sonia S Chicano Eduardo E Úbeda-Banon Isabel I Flores-Cuadrado Alicia A Giménez-Llort Lydia L Alcaín Francisco Javier FJ Peinado Juan Ramón JR Durán-Prado Mario M

Antioxidants (Basel, Switzerland) 20230319 3

Despite its robust proteopathic nature, the spatiotemporal signature of disrupted protein modules in sporadic Alzheimer's disease (AD) brains remains poorly understood. This considered oxidative stress contributes to AD progression and early intervention with coenzyme Q10 or its reduced form, ubiquinol, delays the progression of the disease. Using MALDI-MSI and functional bioinformatic analysis, we have developed a protocol to express how deregulated protein modules arise from hippocampus and co ...[more]

PMID: 36978996

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Project description:OBJECTIVE: To understand the molecular pathways underlying the cardiac preconditioning effect of short-term caloric restriction (CR). BACKGROUND: Lifelong CR has been suggested to reduce the incidence of cardiovascular disease through a variety of mechanisms. However, prolonged adherence to a CR life-style is difficult. Here we show how short-term CR protects the mouse heart from ischemia. METHODS: Male 10-12 wk old C57bl/6 mice were randomly assigned to an ad libitum (AL) diet with free access to regular chow, or CR, receiving 30% less food over a period of 7 days (d), prior to myocardial infarction (MI) via permanent coronary ligation. Prior to MI (d8), the left ventricles (LV) of AL and CR mice were collected for Western blot, DNA and microRNA (miR) analyses. In separate groups, infarct size, cardiac hemodynamics and protein abundance of caspase 3 was measured at d2 post-MI. RESULTS: This short-term model of CR was associated with cardio-protection, as evidenced by decreased infarct size (18.5±2.4% vs. 26.6±1.7%, N=10/group; P=0.01). cDNA and miR profiles pre-MI (N=5/group) identified genes modulated by short-term CR to be associated with circadian clock, oxidative stress, immune function, apoptosis, metabolism, angiogenesis, cytoskeleton and extracellular matrix (ECM). Western blots pre-MI revealed CR-associated increases in phosphorylated Akt and GSK3ß, reduced levels of phosphorylated AMPK and mitochondrial related proteins PGC-1?, cytochrome C and cyclooxygenase (COX) IV, with no differences in the levels of phosphorylated eNOS or MAPK (ERK1/2; p38). CONCLUSIONS: Short-term CR for only 7d represents a preconditioning strategy that limits infarct size. It is associated with a unique gene and miR signature, including the activation of specific pro-survival kinases. These findings may have implications for therapeutic use of short-term CR. . Male 12 wk-old C57Bl/6 mice were obtained from Charles River (Montreal, PQ, Canada) and maintained for at least 2 weeks before experimentation. Animals were randomly assigned to AL, CR and Lira groups with no initial differences in body weights. AL group mice were allowed ad libitum diet. Lira group mice were injected with Liraglutide (Glucagon-like peptide-1 agonist) at a dose of 200 µg/Kg i.p., twice daily for 7 days which is a mild weight-loss inducing dose and had access to ad libitum food and water. CR group mice were put on a Caloric restriction diet (30% less than normal ad libitum caloric intake) for 7 days to induce weight loss comparable to Lira group mice. Mice for CR and AL were individually caged and their food intake was measured everyday between 10-11 am for 1 week to calculate the average daily food intake. CR mice were fed 30% less than the calculated mean daily AL food consumption. CR cages were inspected daily for any remaining food, and transferred to a new cage every day. For CR group, pre-weighed mouse chow pellets were placed in cages between 10-11 am every day. Body weights were recorded between 10-11 am before and after the 7 day study period. For pre-ischemic assessments, animals (n=5/group/assessment) were sacrificed on day-8 (pre-MI), hearts were immediately extracted, washed in sterile phosphate-buffered saline (PBS), with LV free walls dissected, snap frozen in liquid nitrogen and stored at -80o C.

Dataset Information

Comprehensive evaluation of Ubiquinol-supplemented diet effects in the 3xTg AD mice using MALDI-MSI

Publications

Spatial and Temporal Protein Modules Signatures Associated with Alzheimer Disease in 3xTg-AD Mice Are Restored by Early Ubiquinol Supplementation.

Similar Datasets

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