Changes in RNA Splicing: A New Paradigm of Transcriptional Responses to Probiotic Action in the Mammalian Brain

Microorganisms, Journal Year: 2025, Volume and Issue: 13(1), P. 165 - 165

Published: Jan. 14, 2025

Elucidating the gene regulatory mechanisms underlying gut–brain axis is critical for uncovering novel interaction pathways and developing therapeutic strategies gut bacteria-associated neurological disorders. Most studies have primarily investigated how bacteria modulate host epigenetics expression; their impact on alternative splicing, particularly in brain, remains largely unexplored. Here, we effects of gut-associated probiotic Lacidofil® splicing across 10 regions rat brain using published RNA-sequencing data. The altogether altered 2941 differential events, predominantly, skipped exon (SE) mutually exclusive (MXE) events. Protein–protein interactions a KEGG analysis differentially spliced genes (DSGs) revealed consistent enrichment spliceosome vesicle transport complexes, as well related to neurodegenerative diseases, synaptic function plasticity, substance addiction regions. Using PsyGeNET platform, found that DSGs from locus coeruleus (LConly), medial preoptic area (mPOA), ventral dentate gyrus (venDG) were enriched depression-associated or schizophrenia-associated genes. Notably, highlight App gene, where precisely regulated two exons causally involved amyloid β protein-based diseases. Although factors exhibited both plasticity expression response Lacidofil®, overlap between expressed (DEGs) most was rather low. Our study provides mechanistic insight into probiotics might influence through modulation RNA splicing.

Language: Английский

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Lysosomal Ion Channels and Transporters: Recent Findings, Therapeutic Potential, and Technical Approaches

Bioelectricity, Journal Year: 2025, Volume and Issue: 7(1), P. 29 - 57

Published: March 1, 2025

In recent years, there has been a growing interest in lysosomal ion channels and transporters due to their critical role maintaining function involvement variety of diseases, particularly storage cancer, neurodegenerative disorders. Recent advancements research techniques, including manual automated patch clamp (APC) electrophysiology, solid-supported membrane-based electrophysiology (SSME), fluorescence-based imaging, have further enhanced our ability investigate both physiological pathological conditions, spurring drug discovery efforts. Several pharmaceutical companies are now developing therapies aimed at modulating these improve disease. Small molecules targeting like transient receptor potential mucolipin (TRPML) 1 TMEM175, as well drugs pH, currently preclinical clinical development. This review provides an overview the health disease, highlights cutting-edge techniques used study them, discusses therapeutic treatment various diseases. Furthermore, addition summarizing discoveries, we contribute novel functional data on cystinosin, TRPML1, two-pore channel 2 (TPC2), utilizing SSME APC approaches.

Language: Английский

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Brain maps of general cognitive function and spatial correlations with neurobiological cortical profiles

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 17, 2024

In this paper, we attempt to answer two questions: 1) which regions of the human brain, in terms morphometry, are most strongly related individual differences domain-general cognitive functioning (g)? and 2) what underlying neurobiological properties those regions? We meta-analyse vertex-wise g-cortical morphometry (volume, surface area, thickness, curvature sulcal depth) associations using data from 3 cohorts: UK Biobank (UKB), Generation Scotland (GenScot), Lothian Birth Cohort 1936 (LBC1936), with meta-analytic N = 38,379 (age range 44 84 years old). These g-morphometry vary magnitude direction across cortex (|β| -0.12 0.17 measures) show good cross-cohort agreement (mean spatial correlation r 0.57, SD 0.18). Then, address (2), bring together existing - derive new cortical maps 33 characteristics multiple modalities (including neurotransmitter receptor densities, gene expression, functional connectivity, metabolism, cytoarchitectural similarity). discover that these profiles spatially covary along four major dimensions organisation (accounting for 65.9% variance) denote aspects scaffolding underpin patterning MRI-cognitive observe (significant |r| 0.21 0.56). Alongside analyses, make openly accessible, provide a compendium cortex-wide within-region correlations among general specific facets brain higher order functioning, hope will serve as framework analysing other behaviour-brain MRI associations.

Language: Английский

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Genome-wide methylome-based molecular pathologies associated with depression and suicide

Neuropsychopharmacology, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 7, 2024

Abstract Major depressive disorder (MDD) is a debilitating disorder. Suicide attempts are 5-times higher in MDD patients than the general population. Interestingly, not all develop suicidal thoughts or complete suicide. Thus, it important to study risk factors that can distinguish suicidality among patients. The present examined if DNA methylation changes behavior depressed subjects. Genome-wide was dorsolateral prefrontal cortex of suicide (MDD+S; n = 15), non-suicide (MDD−S; 17), and nonpsychiatric control (C; 16) subjects using 850 K Infinium Methylation EPIC BeadChip. significantly differentially methylated genes were used determine functional enrichment for ontological clustering pathway analysis. Based on number CpG content their relative distribution from specific landmark regions genes, 32,958 sites identified across 12,574 C vs. MDD+/−S subjects, 30,852 12,019 MDD−S, 41,648 13,941 MDD+S, 49,848 15,015 MDD−S MDD+S groups. A comparison showed 33,129 unique 5451 group compared group. Functional analysis suggested oxytocin, GABA, VGFA, TNFA, mTOR pathways associated with Altogether, our data show distinct pattern methylation, genomic sites, gene enrichment,

Language: Английский

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