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Fiori, L.

Publications and source records attributed to Fiori, L..

5 recordsLinked to original sources

A glucocorticoid-responsive polygenic signature in the anterior cingulate cortex moderates the association of early-life adversity and vulnerability for depression

Stress exposure is a major risk factor for psychopathology, yet how stress mediators shape long-term psychiatric vulnerability in humans remains unclear. Glucocorticoids, central effectors of the stress response, regulate gene expression through tissue-specific transcriptional programs, suggesting that glucocorticoid-responsive networks may shape sensitivity to adversity. Using RNA-sequencing following chronic glucocorticoid exposure in a non-human primate model, we identified a gene co-expression network specific to the anterior cingulate cortex (ACC) that was highly preserved across human post-mortem brain datasets relevant to depression. We derived an expression-based polygenic score (ePGS) reflecting genetic variation in network activity and tested its interaction with adversity in the UK Biobank. The ACC-specific glucocorticoid-responsive ePGS moderated the association between adversity and depressive symptoms in adult females, with the strongest effects for early-life adversity. Network genes were enriched for neurodevelopmental processes and showed stronger co-expression during childhood, highlighting a developmentally sensitive, region-specific mechanism linking stress exposure to depression risk.

neuroscience↗

Balancing postural control and motor inhibition during gait initiation

This study examines the relationship between stopping a planned gait initiation due to sudden environmental changes and maintaining body stability. Using a gait initiation version of the Stop Signal Task (SST), we studied changes in anticipatory postural adjustments (APA) during gait initiation and suppression. We found that trial-level variables, such as the time to start or stop stepping, interacted with biomechanical factors like the center of mass displacement relative to the base of support, affecting performance. A critical biomechanical threshold was identified, beyond which stopping movement was unlikely. These findings highlight the strong link between limb action control and body equilibrium, offering a framework within a motor control paradigm. By integrating biomechanical elements, the model effectively simulates real-life scenarios, identifying key variables for studying neural correlations between action and postural control, and aiding in the development of injury prevention and rehabilitation tools for individuals with movement and posture impairments.

neuroscience↗

Cell type specific transcriptomic differences in depression show similar patterns between males and females but implicate distinct cell types and genes

Major depressive disorder (MDD) is a common, heterogenous, and potentially serious psychiatric illness. Diverse brain cell types have been implicated in MDD etiology. Significant sexual differences exist in MDD clinical presentation and outcome, and recent evidence suggests different molecular bases for male and female MDD. We evaluated over 160,000 nuclei from 71 female and male donors, leveraging new and pre-existing single-nucleus RNA-sequencing data from the dorsolateral prefrontal cortex. Cell type specific transcriptome-wide threshold-free MDD-associated gene expression patterns were similar between the sexes, but significant differentially expressed genes (DEGs) diverged. Among 7 broad cell types and 41 clusters evaluated, microglia and parvalbumin interneurons contributed the most DEGs in females, while deep layer excitatory neurons, astrocytes, and oligodendrocyte precursors were the major contributors in males. Further, the Mic1 cluster with 38% of female DEGs and the ExN10_L46 cluster with 53% of male DEGs, stood out in the meta-analysis of both sexes.

neuroscience↗

One more avenue for whale-watching contributions to science: the study of cetacean-cephalopod interactions

Cephalopods are the primary source of food for several species of odontocetes. The unstable nature of this trophic resource is likely to affect the ecology of their cetacean predators, and this can be reflected on their conservation status but also on the tourist activities which target the observation of these animals. However, the study of the cetacean-cephalopod interaction is limited by the heavy logistics and expense of dedicated scientific campaigns. Fortunately, this gap can be filled by coupling modern molecular tools with indirect sampling methods. In this note we test if whale watching activities, which represent an intense observation effort worldwide, could be a source of material for studies of cetacean-cephalopod interactions. All contacted companies welcomed the invitation and received the sampling kit. Nine samples were collected, most of them in close association with sperm whales. All samples were determined as the seven-arm octopus Haliphron atlanticus (Octopoda, Alloposidae). We conclude that, although the Azores may have particularly favorable conditions for participatory science, similar programs can be replicated elsewhere

ecology↗

Neuron-derived extracellular vesicles extracted from plasma show altered size and miRNA cargo as a function of antidepressant drug response

Previous work has demonstrated that microRNAs (miRNAs) change as a function of antidepressant treatment (ADT) response. However, it is unclear how representative these peripherally detected miRNA changes are to those occurring in the brain. This study aimed to use peripherally extracted neuron-derived extracellular vesicles (NDEVs) to circumvent these limitations and investigate neuronal miRNA changes associated with antidepressant response. Samples were collected at two time points (baseline and after 8 weeks of follow-up) from depressed patients who responded (N=20) and did not respond (N=20) to escitalopram treatment, as well as controls (N=20). Total extracellular vesicles (EVs) were extracted from plasma, and then further enriched for NDEVs by immunoprecipitation with L1CAM. EV size was measured using tunable resistive pulse sensing, and NDEV miRNA cargo was extracted and sequenced. Subsequently, studies in cell lines and postmortem tissue were conducted. Characterization of NDEVs revealed they were smaller than other EVs isolated from plasma (p<0.0001), had brain-specific neuronal markers, and contained miRNAs enriched for brain functions (p<0.0001) Furthermore, NDEVs from depressed patients were smaller than controls (p<0.05), and NDEV size increased with ADT response (p<0.01). Finally, changes in NDEV cargo, specifically changes in miR-21-5p, miR-30d-5p and miR-486-5p together (p<0.01), were associated with ADT response. Targets of these three miRNAs were altered in brain tissue from depressed individuals (p<0.05). Together, this study indicates that changes in peripherally isolated NDEVs can act as both a clinically accessible and informative biomarker of ADT response specifically through size and cargo.

neuroscience↗