Hunger Games: A Modern Battle Between Stress and Appetite

Journal of Neurochemistry, Год журнала: 2025, Номер 169(2)

Опубликована: Фев. 1, 2025

ABSTRACT Stress, an evolutionarily adaptive mechanism, has become a pervasive challenge in modern life, significantly impacting feeding‐relevant circuits that play role the development and pathogenesis of eating disorders (EDs). Stress activates hypothalamic–pituitary–adrenal (HPA) axis, disrupts specific neural circuits, dysregulates key brain regions, including hypothalamus, hippocampus, lateral septum. These particular structures are interconnected integrating stress feeding signals, modulating hunger, satiety, cognition, emotional coping behaviors. Here we discuss interplay between genetic predispositions environmental factors may exacerbate ED vulnerability. We also highlight most commonly used animal models to study mechanisms driving EDs recent rodent studies emphasize discovery novel cellular molecular signals within hippocampus–lateral septum–hypothalamus axis. In this review, gut microbiome, emerging area research field unanswered questions persist hinder scientific progress, such as why some individuals remain resilient while others at high risk for EDs. finally need future delineating impact stressors on clarifying relevance functionality hippocampal–septal–hypothalamic connectivity, investigating neuropeptides CRH, oxytocin, GLP‐1 human pathogenesis. Emerging tools like single‐cell sequencing advanced imaging could uncover circuit‐level changes areas relevant patients. Ultimately, by basic clinical research, science offers promising avenues developing personalized, mechanism‐based treatments targeting maladaptive behavior patients suffering from image

Язык: Английский

A dorsal hippocampus-prodynorphinergic dorsolateral septum-to-lateral hypothalamus circuit mediates contextual gating of feeding

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Авг. 6, 2024

SUMMARY Adaptive regulation of feeding depends on linkage internal states and food outcomes with contextual cues. Human brain imaging has identified dysregulation a hippocampal-lateral hypothalamic area (LHA) network in binge eating, but mechanistic instantiation underlying cell-types circuitry is lacking. Here, we identify an evolutionary conserved discrete Prodynorphin ( Pdyn )-expressing subpopulation Somatostatin Sst inhibitory neurons the dorsolateral septum (DLS) that receives primarily dorsal, not ventral, hippocampal inputs. DLS( ) inhibit LHA GABAergic confer context- state-dependent calibration feeding. Viral deletion DLS mimicked effects seen optogenetic silencing INs, suggesting potential role for DYNORPHIN-KAPPA OPIOID RECEPTOR signaling food-seeking. Together, our findings illustrate how dorsal hippocampus evolved to recruit ancient circuit module through link information consumption. HIGHLIGHTS receive dense input from ventral Silencing hippocampus-DLS( )-LHA nodes abolishes context-conditioned necessary

Язык: Английский

INSTINCT: Multi-sample integration of spatial chromatin accessibility sequencing data via stochastic domain translation

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Май 31, 2024

Abstract Recent advances in spatial epigenomic techniques have given rise to assay for transposase-accessible chromatin using sequencing (spATAC-seq) data, enabling the characterization of heterogeneity and information simultaneously. Integrative analysis multiple spATAC-seq samples, which no method has been developed, allows effective identification elimination unwanted non-biological factors within comprehensive exploration tissue structures providing a holistic landscape, thereby facilitating discovery biological implications study regulatory processes. In this article, we present INSTINCT, multi-sample INtegration Spatial chromaTIN accessibility data via stochastiC domain Translation. INSTINCT can efficiently handle high dimensionality eliminate complex noise batch effects samples from different conditions through stochastic translation procedure. We demonstrate superiority robustness integrating across simulated scenarios real datasets. Additionally, highlight advantages identification, visualization, spot-type annotation, various downstream analyses, including motif enrichment analysis, expression partitioned heritability analysis.

Язык: Английский