Hunger Games: A Modern Battle Between Stress and Appetite DOI Open Access

W. G. Smith,

Estefania P. Azevedo

Journal of Neurochemistry, Journal Year: 2025, Volume and Issue: 169(2)

Published: Feb. 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

Language: Английский

Central regulation of stress-evoked peripheral immune responses DOI
Kenny L. Chan, Wolfram C. Poller, Filip K. Świrski

et al.

Nature reviews. Neuroscience, Journal Year: 2023, Volume and Issue: 24(10), P. 591 - 604

Published: Aug. 25, 2023

Language: Английский

Citations

71
Circulating myeloid-derived MMP8 in stress susceptibility and depression DOI Creative Commons
Flurin Cathomas, Hsiao‐Yun Lin, Kenny L. Chan

et al.

Nature, Journal Year: 2024, Volume and Issue: 626(8001), P. 1108 - 1115

Published: Feb. 7, 2024

Abstract Psychosocial stress has profound effects on the body, including immune system and brain 1,2 . Although a large number of pre-clinical clinical studies have linked peripheral alterations to stress-related disorders such as major depressive disorder (MDD) 3 , underlying mechanisms are not well understood. Here we show that expression circulating myeloid cell-specific proteinase, matrix metalloproteinase 8 (MMP8), is increased in serum humans with MDD stress-susceptible mice following chronic social defeat (CSDS). In mice, this increase leads extracellular space neurophysiological changes nucleus accumbens (NAc), altered behaviour. Using combination mass cytometry single-cell RNA sequencing, performed high-dimensional phenotyping cells circulation demonstrate monocytes strongly affected by stress. both traffic showed Mmp8 We further MMP8 directly infiltrates NAc parenchyma controls ultrastructure space. Depleting prevented stress-induced avoidance behaviour neurophysiology Collectively, these data establish mechanism which factors can affect central nervous function context Targeting specific cell-derived metalloproteinases could constitute novel therapeutic targets for neuropsychiatric disorders.

Language: Английский

Citations

62
Neurobiological basis of stress resilience DOI
Eric J. Nestler, Scott J. Russo

Neuron, Journal Year: 2024, Volume and Issue: 112(12), P. 1911 - 1929

Published: May 24, 2024

Language: Английский

Citations

27
Transcriptomic characterization of human lateral septum neurons reveals conserved and divergent marker genes across species DOI Creative Commons
Robert A. Phillips, Seyun Oh, Svitlana V. Bach

et al.

iScience, Journal Year: 2025, Volume and Issue: 28(2), P. 111820 - 111820

Published: Jan. 18, 2025

The lateral septum (LS) is a midline, subcortical structure that critical regulator of social behaviors. Mouse studies have identified molecularly distinct neuronal populations within the LS, which control specific facets behavior. Despite its known molecular heterogeneity in mouse and role regulating behavior, comprehensive profiling human LS has not been performed. Here, we conducted single-nucleus RNA sequencing (snRNA-seq) to generate transcriptomic profiles compared recently collected snRNA-seq datasets. Our analyses TRPC4 as conserved marker while FREM2 enriched only LS. We also identify cell type marked by OPRM1, gene encoding μ-opioid receptor. Together, these results highlight transcriptional robust genes for

Language: Английский

Citations

2
Parsing the heterogeneity of social motivation in autism DOI Open Access
Lacey Chetcuti, Antonio Y. Hardan, Emily Spackman

et al.

Journal of Child Psychology and Psychiatry, Journal Year: 2025, Volume and Issue: unknown

Published: March 16, 2025

Background Social motivation is posited as a key factor in the expression of autism phenotype. However, lack precision both conceptualization and measurement has impeded thorough understanding its diverse presentation associated outcomes. This study addresses this gap by identifying subgroups characterized deficits distinct facets social motivation, relative to normative benchmarks. Methods Data were from 509 participants with autism, aged 5‐to‐21 years ( M = 10.43, SD 3.67; 81% male), enrolled Healthy Brain Network. Latent profile analysis was employed identify unique configurations reticence, seeking, maintaining derived comprehensive multi‐instrument symptom screening measures. Pearson's chi‐square tests one‐way variance performed explore subgroup differences demographic characteristics, cognitive abilities, co‐occurring psychopathologies, other aspects functioning. Results Four identified: Engaged n 247), exhibiting fewest challenges across each area; Inhibited 143), high mild few maintaining; Aloof 68), seeking but relatively low reticence; Avoidant 52), highest all areas. Subgroups did not differ terms chronological age or sex. The exhibited functioning while greatest challenges, profiles falling between. Conclusions highlights heterogeneous nature benchmarks, suggesting potential avenues for tailored interventions aimed at addressing specific experienced individuals within subgroup. Nevertheless, there remains need develop more refined tools capable capturing even finer‐grained expressions facilitating further characterization individual diagnostic boundaries.

Language: Английский

Citations

2
Cellular and circuit architecture of the lateral septum for reward processing DOI
Gaowei Chen,

Shishi Lai,

Shaolei Jiang

et al.

Neuron, Journal Year: 2024, Volume and Issue: 112(16), P. 2783 - 2798.e9

Published: July 2, 2024

Language: Английский

Citations

9
A crucial role for the cortical amygdala in shaping social encounters DOI Creative Commons
Antonio Aubry, Romain Durand-de Cuttoli,

Elizabeth Karpman

et al.

Nature, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 12, 2025

Language: Английский

Citations

1
Protein Design Accelerates the Development and Application of Optogenetic Tools DOI Creative Commons

Lingyun Zhu,

Yuxuan Wang, Xiaomin Wu

et al.

Computational and Structural Biotechnology Journal, Journal Year: 2025, Volume and Issue: 27, P. 717 - 732

Published: Jan. 1, 2025

Optogenetics has substantially enhanced our understanding of biological processes by enabling high-precision tracking and manipulation individual cells. It relies on photosensitive proteins to monitor control cellular activities, thereby paving the way for significant advancements in complex system research. Photosensitive play a vital role development optogenetics, facilitating establishment cutting-edge methods. Recent breakthroughs protein design have opened up opportunities develop protein-based tools that can precisely manipulate activities. These will significantly accelerate application optogenetic tools. This article emphasizes pivotal tools, offering insights into potential future directions. We begin providing an introduction historical fundamental principles followed exploration operational mechanisms key domains, which includes clarifying conformational changes they undergo response light, such as allosteric modulation dimerization processes. Building this foundation, we reveal enable creation even more sophisticated techniques.

Language: Английский

Citations

1
Single-Cell Resolution of Individual Variation in Hypothalamic Neurons Allows Targeted Manipulation Affecting Social Motivation DOI Creative Commons
Simona Sarafinovska, Sarah K. Koester,

Li Fang

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: March 12, 2025

Abstract Despite decades of research, connecting molecular and cellular phenotypes to complex behavioral traits remains an elusive goal 1 . Social motivation exhibits individual trait variation 2 , which we hypothesize is mediated by variability across hypothalamic neurons. To test this, generated single-nucleus RNA-sequencing profiles 3,4 >120,000 neurons from tuberal hypothalamus adjacent thalamus in 36 mice, balanced sex autism-associated mutation 5 with all mice assessed for social First, show that activation patterns predict behavior individuals: specifically, paraventricular Agtr1a + (angiotensin receptor 1a) predicted reduced behavior. Subsequent inhibition AGTR1A telmisartan—an FDA-approved antihypertensive 6 —improved orienting. Second, natural neuronal proportions—likely arising stochastic developmental events 7 —is sufficient shape adult even among genetically-identical identified multiple populations whose relative abundance reward-seeking Chemogenetic one such population, Nxph4 the postero-lateral 8 suppressed aspects motivation. This work establishes proof-of-principle approach where single-cell genomics precisely maps neural substrates governing revealed variations architecture deterministically influence motivation, enabled identification therapeutically-actionable targets immediate translational potential disorders deficits.

Language: Английский

Citations

1
Stress dynamically modulates neuronal autophagy to gate depression onset DOI Creative Commons
Liang Yang, Guo Chen, Zhi-Wei Zheng

et al.

Nature, Journal Year: 2025, Volume and Issue: unknown

Published: April 9, 2025

Chronic stress remodels brain homeostasis, in which persistent change leads to depressive disorders1. As a key modulator of homeostasis2, it remains elusive whether and how autophagy is engaged dynamics. Here we discover that acute activates, whereas chronic suppresses, mainly the lateral habenula (LHb). Systemic administration distinct antidepressant drugs similarly restores function LHb, suggesting LHb as common target. Genetic ablation neuronal promotes susceptibility, enhancing exerts rapid antidepressant-like effects. controls excitability, synaptic transmission plasticity by means on-demand degradation glutamate receptors. Collectively, this study shows causal role maintaining emotional homeostasis against stress. Disrupted implicated maladaptation stress, its reversal enhancers provides new strategy.

Language: Английский

Citations

1