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Merienne, K.

Publications and source records attributed to Merienne, K..

3 recordsLinked to original sources

Systematic review and transcriptomic meta-analysis of environmental enrichment reveal core molecular programs of brain plasticity

RATIONALEEnvironmental enrichment (EE) paradigms in rodents have long demonstrated that enhanced sensory, cognitive, social, and motor stimulation positively impacts brain function, improving learning, memory, and neuroplasticity. These effects have significant implications for understanding cognitive development and mitigating cognitive decline and brain aging. While numerous transcriptomic studies have explored EE-induced molecular changes, a unified view of the genes and pathways consistently modulated remains lacking. METHODSTo address this gap, we performed a systematic review and meta-analysis. We conducted a comprehensive PubMed search for all studies published up to February 2025 that matched all the following inclusion criteria: (1) employed EE paradigms; (2) were conducted on rodents; (3) utilized genome-wide transcriptomic methods; (4) examined brain regions or neuronal populations. The 323 retrieved articles were manually screened for relevance to the study aims and data availability. Datasets from 20 eligible RNA-seq reports were reprocessed using a unified analysis pipeline and subjected to a meta-analysis with three complementary statistical methods. RESULTSDespite considerable heterogeneity across studies, our integrative analysis identified consistent gene expression signatures linked to synaptic function, plasticity and their transcriptional regulation. These molecular insights advance our understanding of how EE impacts on neuronal and behavioural outcomes, and may inform therapeutic strategies aimed at replicating or enhancing EE benefits. To promote open science and foster further research, we developed an accessible web application, mEEtaBrain, that enables the neuroscience community to navigate and interrogate our meta-analysis results.

neuroscience↗

Sex-divergent brain epigenetic reprogramming by chronic opioids

Opioid use disorder (OUD) is a chronic condition that exhibits sex differences in prevalence, symptoms and treatment. Yet, the epigenetic mechanisms underlying these differences remain largely unknown. Here, we investigated the nucleus accumbens, a key brain region in OUD, to define the multiomic consequences of chronic morphine exposure in male and female mice. We profiled DNA methylation, five histone post-translational modifications, and their transcriptional effects at bulk and cell-type-specific levels. Despite comparable tissue organization and neurophysiological responses to morphine, epigenetic adaptations occurred at highly sex-specific genomic loci. These adaptations nevertheless followed common mechanistic principles, acting at similar gene features and transcription factor binding sites across sexes. Strikingly, they converged on overlapping genes, biological functions, and co-expression modules, and partially recapitulated transcriptional signatures of OUD in men and women. Therefore, our findings uncover a profound epigenetic sex divergence that mediates convergent biological dysregulation, and highlight opportunities for developing improved therapeutic strategies tailored to sex-specific mechanisms.

neuroscience↗

Mind Your Spectra: Points to be Aware of when Validating the Identification of Isobaric Histone Peptidoforms

Mass spectrometry (MS) has become a central technique to identify and quantify post-translational modifications (PTMs), overcoming limitations of antibody-based methods. Histones get dynamically modified by diverse chemical groups, particularly on their numerous lysine residues, to fine-tune all DNA-templated processes. Reliable identification of histone PTMs remains challenging and still requires manual data curation. This study focused on the Lys27-Arg40 stretch of histone H3, considered four sequence variants, an increasing number of lysine PTMs and artifacts coming from histone sample processing, which resulted in many peptides with the same atomic composition. Our analysis revealed the value of low-mass b1 and cyclic immonium fragment ions to validate identification of the distinct peptidoforms. We examined how MS/MS spectra are transformed by common software tools during the conversion of RAW files into peak lists, and highlighted how some parameters may erase the informative low-mass fragments. We established the fragmentation profiles and retention times for forty H3 K27-R40 variantxPTM combinations, including the mouse-specific variants H3mm7 and H3mm13, and targeted their detection in histone samples extracted from mouse testis and brain via a scheduled parallel reaction monitoring (PRM) analysis. The transcripts of these two mousespecific variants were reported to be highly abundant in these tissues and the corresponding proteins may seem to be identified by data-dependent analyses. However, we only detected very low levels of the unmodified form of H3mm7 and found no trace of H3mm13 by PRM. Our work contributes to reliably deciphering the histone code shaped by distinct sequence variants and numerous combinations of PTMs.

biochemistry↗