Biology subjects

Mendioroz, M.

Publications and source records attributed to Mendioroz, M..

3 recordsLinked to original sources

bioRxiv2025

Dynamic methylation changes in Alzheimers disease-related genes during mindfulness practice - a proof-of-concept study

BackgroundMindfulness meditation has gained significant attention in the context of Alzheimers disease (AD) due to its potential effects on the prevention of cognitive decline and overall psychological well-being. The epigenetic landscape of this complex neurodegenerative disorder can be influenced by environmental factors. Mindfulness practices could actively shape the biological response to AD by modifying the underlying molecular mechanisms through epigenetic regulation. MethodsA group of 17 long-term mindfulness meditators (MMs) and 17 sex- and age-matched controls were recruited. Experienced MMs participated in a 1-month Vipassana meditation retreat. Blood DNA methylation levels of differentially methylated genes (ABCA7, ADAM10, APOE, HOXA3, NXN, TREM2 and TREML2) previously validated in a predictive AD-model found analyzed by bisulfite pyrosequencing. ResultsAn increase in DNA methylation was observed for ADAM10, APOE, HOXA3 and TREM2 in MMs with respect to controls. Furthermore, significant differences were found for ABCA7, ADAM10, APOE and HOXA3 in MMs after retreat. ConclusionsDNA methylation changes identified for ADAM10 and HOXA3 in MMs are in the opposite direction to those occurring in AD and may constitute a protective epigenetic alteration. Mindfulness practice could counteract DNA methylation of key AD genes as a possible preventive strategy or non-pharmacological intervention in AD patients.

neuroscience↗

bioRxiv2021

A TREM2-derived circRNA is upregulated in the entorhinal cortex of Alzheimer's disease patients

Circular RNAs (circRNAs) are a novel class of noncoding RNAs characterized by a covalent and stable closed loop structure. circRNAs are enriched in neural tissues, particularly at synapses, where they are involved in synaptic plasticity. Alzheimers disease (AD) is considered a synaptopathy since neurodegeneration causes loss or dysfunction of synapses. Microglia participate in synaptic pruning and also play a crucial role in developing AD. For instance, genetic variants in TREM2, a microglia-related gene, are risk factors for AD. Alterations in circRNAs expression have been described in different neurological diseases, including AD. However, no TREM2-derived circRNAs have been described so far. TREM2 has 3 linear RNA variants due to alternative splicing. We hypothesized that alternative splicing of exon 4 might be favoring circRNAs originating from TREM2 (circTREM2s), which in turn might be involved in AD pathogenesis. First, divergent primers (overlapping exons 3-4 and 4-5) were designed to amplify circRNAs by RT-PCR, which were confirmed by Sanger sequencing. Three candidate TREM2-derived circRNAs were identified on control human entorhinal samples. Then, additional primer sets were used to confirm back-splicing junctions. One of the circRNAs, circTREM2_1, was consistently amplified with all primer sets. In addition, circTREM2_1 was also present in AD entorhinal cortex samples and in HMC3 cells. We observed that circTREM2_1 is up-regulated in AD entorhinal cortex samples compared to controls, particularly at early stages of the disease, when we performed RT-qPCR. In conclusion, we have identified a novel circRNA derived from the TREM2 gene that could play a role in AD pathogenesis.

genetics↗

bioRxiv2020

Molecular markers characterization determining cell fate specification in an adult neurogenesis model of Alzheimer's disease

Adult hippocampal neurogenesis (AHN) study is still a challenge. In addition to methodological difficulties is the controversy of results derived of human or animal system approaches. In view of the proven link between AHN and learning and memory impairment, we generated a straightforward in vitro model to recapitulate adult neurogenesis in the context of Alzheimer's disease (AD). Neural progenitor cells (NPCs) monolayer culture was differentiated for a period of 29 days and A{beta} peptide 1-42 was administered once a week. mRNA expression of NEUROD1, NCAM1, TUBB3, RBFOX3, CALB1 and GFAP genes was determined by RT-qPCR. Phenotypic changes were observed during directed differentiation. Except for GFAP and CALB1, these changes correlated with altered expression profile of all genes since 9 days. Only TUBB3 expression remained constant while NEUROD1, NCAM1 and RBFOX3 expression increased over time. Moreover, A{beta} treated NPCs showed transient decreases of mRNA expression for NCAM1, TUBB3 and RBFOX3 genes at 9 or 19 days. Our in vitro human NPCs model is framed within the multistep process of AHN in the SGZ of the DG. Remarkably, its transcriptional assessment might reflect alterations detected in AD human patients, deepening our understanding of the disorder and possibly of its pathogenesis.

neuroscience↗