Biology subjects

Moran, K. L.

Publications and source records attributed to Moran, K. L..

3 recordsLinked to original sources

bioRxiv2026

Early life stress alters lifespan trajectories of amygdala development: a cross-species model of amygdala burnout

Early-life stress is associated with alterations in amygdala volume, but findings vary across studies and species. Rodent models typically report increased amygdala volume, whereas human studies often find reductions or mixed effects. We propose the amygdala burnout hypothesis, which suggests that early-life stress alters amygdala developmental trajectories, producing initial volumetric increases that are followed by reductions later in life. To test this hypothesis, we examined amygdala development across rodent and human cohorts spanning adolescence to older adulthood. In rodents, chronic stress was associated with increased amygdala nuclei volumes during adolescence. Comparable increases were observed in adolescents from the IMAGEN consortium, with evidence of a dose-dependent association between childhood stress and amygdala developmental trajectories. In contrast, analyses of older adults from the UK Biobank revealed reduced bilateral amygdala volume associated with early-life stress. Together, these findings support a developmental model that reconciles previously conflicting observations across species and age groups. Early-life stress is associated with alterations in amygdala volume, but findings vary across studies and species. Rodent models typically report increased amygdala volume, whereas human studies often find reductions or mixed effects. We propose the amygdala burnout hypothesis, which suggests that early-life stress alters amygdala developmental trajectories, producing initial volumetric increases that are followed by reductions later in life. To test this hypothesis, we examined amygdala development across rodent and human cohorts spanning adolescence to older adulthood. In rodents, chronic stress was associated with increased amygdala nuclei volumes during adolescence. Comparable increases were observed in adolescents from the IMAGEN consortium, with evidence of a dose-dependent association between childhood stress and amygdala developmental trajectories. In contrast, analyses of older adults from the UK Biobank revealed reduced bilateral amygdala volume associated with early-life stress. Together, these findings support a developmental model that reconciles previously conflicting observations across species and age groups.

neuroscience↗

bioRxiv2024

Cytoplasmic lncRNAs nucleate signalling pathways to define metastable state dynamics and determine phenotypic output

Cell plasticity, the ability that cells display to rapidly adapt to environmental cues, is thought to be encoded in non-genetic information reservoirs. Although the notion is widely acknowledged, the molecular details underlying this phenomenon remain largely concealed. Herein, we show that clonal cell populations inherently display multiple co-existing metastable gene expression states that co-segregate with various phenotypic outputs. Moreover, we provide primer evidence suggesting that transcriptome states are inherited, dynamically interconvert and determine phenotypic output upon a variety of biological cues, not as a result of transcriptional shifts, but rather through yet unidentified post-transcriptional mechanisms. Remarkably, among phenotypically divergent clonal cell populations enriched in subsets of transcriptome states, we identified a peri-nuclear cytoplasmic structure (Signal Integration Portal - SIP) where state-specific lncRNAs, proteins harbouring intrinsically disordered regions and various active signalling pathways converge. Herein, we propose that SIP-condensates act as nucleating reservoir of non-genetic information at the crossroads of cell plasticity and non-genetic heterogeneity where they integrate intra- and extracellular inputs thereby moulding phenotypic output.

cell biology↗

bioRxiv2024

Cerebrovascular Health Mediates Processing Speed Change Through Anterior White Matter Alterations: A UK Biobank Study

Cerebrovascular disease is associated with an increased likelihood of developing dementia. While cardiovascular risk factors are modifiable and may reduce the risk of later-life cognitive dysfunction, the relationship between cerebrovascular risk factors, brain integrity and cognition remains poorly characterised. Using a large UK Biobank sample of predominantly middle-aged adults, without neurological disease, our structural equation mediation models showed that poor cerebrovascular health, indicated by the presence of cerebrovascular risk factors, was associated with slowed processing speed. This effect was best explained by anterior white matter microstructure changes, rather than posterior changes. Effects were also significantly reduced when considering other forms of cognition, demonstrating both regional- and cognitive-specificity of our effects. Critically, our findings also demonstrate that including measures of risk factor duration may be particularly important for improving estimations of cerebrovascular burden. In summary, our study demonstrates the specific impact of early cerebrovascular burden on brain structure and cognitive function, highlighting the necessary next steps for improving cerebrovascular burden quantification and improving clinical predictions.

neuroscience↗