A Comprehensive Overview of Stress, Resilience, and Neuroplasticity Mechanisms
Abstract
1. Introduction
- External stimuli out of the subject’s control that impose demands on the organism;
- Neural processes that evaluate these demands and available resources;
- Physiological, behavioral, and subjective activations indicative of stress;
- Neuroadaptations in brain systems involved in emotion and motivation under chronic stress;
- Cognitive, physiological, and behavioral adaptations in response to stressors.
2. Stress
2.1. Early-Life Stress
2.1.1. Match/Mismatch Hypothesis
2.1.2. Cumulative Stress Hypothesis
2.1.3. Three-Hit Concept
2.2. Early Stress and Critical Developmental Periods
3. Resilience
3.1. Delimitation of the Concept of Stress Resilience
3.2. Models of Stress Resilience
3.2.1. Selective Breeding
3.2.2. Selection of Subpopulations
3.2.3. Transgenic Models
4. Neuroanatomical Structures and Plasticity Mechanisms Involved in Stress and Resilience Responses
4.1. Reward Circuit
4.2. Reward Circuit, Stress, and Resilience
4.3. Plasticity Mechanisms Associated with Stress and Resilience
5. Conclusions
Author Contributions
Funding
Data Availability Statement
Conflicts of Interest
Abbreviations
ELS | Early-life stress |
HPA | Hypothalamic–pituitary–adrenal axis |
PFC | Prefrontal cortex |
CORT | Corticosterone |
EEG | Electroencephalography |
DNA | Deoxyribonucleic acid |
FST | Forced swimming test |
BDNF | Brain-derived neurotrophic factor |
5-HT | Serotonin |
CMS | Chronic mild stress |
BBB | Blood–brain barrier |
KO | Knockout |
GLU | Modulated glutamate |
VGLUT1 | Vesicular glutamate transporter 1 |
DA | Dopamine |
OPIs | Opioid peptides |
GABA | Gamma-aminobutyric acid |
VTA | Ventral tegmental area |
NA | Norepinephrine |
NAc | Nucleus Accumbens |
Hyp | Hypothalamus |
Hb | Habenula |
LHb | Lateral habenula |
Amy | Amygdala |
Hippo | Hippocampus |
iTRAQ | Isobaric tags for relative and absolute quantitation |
AHN | Adult hippocampal neurogenesis |
NPCs | Neural progenitor cells |
FGF-2 | Fibroblast growth factor 2 |
VEGF | Vascular endothelial growth factor |
IGF-1 | Insulin-like growth factor 1 |
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Dimension | Description | Refs. |
---|---|---|
General Definition | Multifaceted capacity of an organism or individual to adapt, recover, and/or grow after adversity. | [8,72,80] |
Essential Components | Significant risk: exposure to major stressors threatening well-being. Positive adjustment: adaptive response and/or growth following adversity. | [5,72] |
Perspectives of the Concept | Resilience as recovery: return to the preadversity state. Resilience as growth: surpassing the previous level of functioning. Resilience as an adaptive process: dynamic interactions between internal and external factors. | [8,79,80] |
Modulating Factors | Neurobiological factors: efficient regulation of the HPA axis, synaptic plasticity, and allostatic responses. Genetic and epigenetic factors: gene expression is influenced by stress experiences. Environmental and social factors: social support, relationship quality, and resource availability. | [9,74,81] |
Conceptual Differentiation | Invulnerability: absolute resistance (not synonymous with resilience). Stress resistance: coping without necessarily improving. Mental toughness: psychological competency in facing challenges. | [79,80] |
Bidimensional Aspect | Significant risk: magnitude of the adverse event. Positive adjustment: functional positive outcome in social or behavioral contexts. | [72,78] |
Behavioral Indicators | Social avoidance, anhedonia, academic or social success, controlled emotional responses. | [78,81] |
Measurement and Evaluation | Currently based on psychometric scales and subjective reports, with a need for objective methods (e.g., biomarkers). | [5,77] |
Animal Models | Maternal separation Chronic social defeat stress Forced swimming tests | [76,81,82,83] |
Challenges and Limitations | Lack of a unified definition. Limited standardization of evaluation methods. Inadequate use of the term in studies. | [5,74] |
Gene–Environment Interaction | The social environment and genetic predisposition work together to shape resilience responses. | [84,85] |
Future Applications | Development of personalized interventions to foster resilience. Creation of biomarkers for an objective evaluation. Inclusion of interdisciplinary approaches in its study. | [74,78] |
Brain Structure | Synthesized Functions | Refs. |
---|---|---|
Reward System | Controls motivation and pleasure, activated by natural rewards and drugs of abuse. Plasticity in the VTA and NAc modulates reward and counteracts anhedonia from stress. | [103,104,105] |
Ventral Tegmental Area (VTA) | Origin of dopamine for reward and motivation. Projects to limbic and cortical regions. Its volume correlates with post-stress social avoidance. | [103,104,105,112] |
Nucleus Accumbens (NAc) | Key for reward and motivation, receives dopamine signals from the VTA. Its plasticity counteracts anhedonia. Its volume is inversely related to social avoidance. β-Catenin promotes stress resilience. | [121,122] |
Amygdala | Processes emotional responses and stimulus valence. Greater connectivity with the PFC in resilient individuals (better emotional regulation). Its activity increases in chronic stress susceptibility. Dendritic changes due to chronic stress affect fear learning. | [6,40,120,121] |
Hippocampus | Involved in memory and navigation. Its plasticity is related to reward. Its activity is suppressed in chronic stress susceptibility. Its volume correlates with social avoidance. Early stress alters its structure and function (memory, maternal behavior, reduced neurogenesis). Adult neurogenesis influences anxiety and resilience, which is regulated by neurotrophic factors and social experiences. Chronic juvenile stress causes atrophy. | [6,42,120,121,124,125,126,127,128,129,130,131] |
Prefrontal Cortex (PFC) | Involved in executive functions and planning. Greater connectivity with the amygdala is observed in resilient individuals (better emotional regulation). It receives dopamine signals. Its activity is suppressed in individuals with chronic stress resilience and increased in susceptible individuals in specific areas. Its volume is related to social avoidance. Chronic juvenile stress causes atrophy. | [6,40,113,120,121] |
Habenula | Processes negative feedback and aversion. Its volume correlates with social avoidance. BDNF influences cell proliferation in this region. Neurogenesis in this area might buffer stress responses. | [121,132,133,134,135,136] |
Hypothalamus | Regulates the stress response and homeostasis. Its volume correlates with social avoidance. The hippocampus relates to it differently in stress resilience and susceptibility. BDNF may promote neurogenesis in this area. | [121,132] |
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Buenrostro-Jáuregui, M.H.; Muñóz-Sánchez, S.; Rojas-Hernández, J.; Alonso-Orozco, A.I.; Vega-Flores, G.; Tapia-de-Jesús, A.; Leal-Galicia, P. A Comprehensive Overview of Stress, Resilience, and Neuroplasticity Mechanisms. Int. J. Mol. Sci. 2025, 26, 3028. https://doi.org/10.3390/ijms26073028
Buenrostro-Jáuregui MH, Muñóz-Sánchez S, Rojas-Hernández J, Alonso-Orozco AI, Vega-Flores G, Tapia-de-Jesús A, Leal-Galicia P. A Comprehensive Overview of Stress, Resilience, and Neuroplasticity Mechanisms. International Journal of Molecular Sciences. 2025; 26(7):3028. https://doi.org/10.3390/ijms26073028
Chicago/Turabian StyleBuenrostro-Jáuregui, Mario Humberto, Sinuhé Muñóz-Sánchez, Jorge Rojas-Hernández, Adriana Ixel Alonso-Orozco, German Vega-Flores, Alejandro Tapia-de-Jesús, and Perla Leal-Galicia. 2025. "A Comprehensive Overview of Stress, Resilience, and Neuroplasticity Mechanisms" International Journal of Molecular Sciences 26, no. 7: 3028. https://doi.org/10.3390/ijms26073028
APA StyleBuenrostro-Jáuregui, M. H., Muñóz-Sánchez, S., Rojas-Hernández, J., Alonso-Orozco, A. I., Vega-Flores, G., Tapia-de-Jesús, A., & Leal-Galicia, P. (2025). A Comprehensive Overview of Stress, Resilience, and Neuroplasticity Mechanisms. International Journal of Molecular Sciences, 26(7), 3028. https://doi.org/10.3390/ijms26073028