Neurobiological Mechanisms of Stress-Induced Gastric Dysfunction

Stress-induced gastric dysfunction arises from complex interactions within the central autonomic network, whereby psychological and physical stressors trigger neuroendocrine and neurotransmitter pathways that alter gastric motility, secretion and mucosal integrity. Activation of the hypothalamic–pituitary–adrenal axis releases corticotropin‐releasing hormone and glucocorticoids, modulating vagal outflow and sympathetic tone. Key forebrain structures, including the ventromedial hypothalamic nucleus, the central nucleus of the amygdala and the periaqueductal grey, communicate with brainstem autonomic centres to regulate gastric acid secretion and motility via the dorsal vagal complex. Local neural‐glial networks, particularly astrocytes in hypothalamic and brainstem nuclei, shape neuronal excitability and inflammatory signalling, contributing to mucosal vulnerability. Dysregulation of kinase cascades such as extracellular signal‐regulated kinase (ERK1/2) further amplifies cellular stress responses within central gastric control circuits. Collectively, these mechanisms underlie the pathophysiology of stress‐related gastritis, peptic ulcers and functional dyspepsia, with broad implications for stress management and therapeutic targeting of central pathways to preserve gastric health.

Research from Nature Portfolio

Recent studies have elucidated the pivotal role of the ventromedial hypothalamic nucleus in moderating gastric responses to acute stress. Experimental lesions in this nucleus intensified gastric mucosal injury following restraint water‐immersion stress by enhancing acid secretion and motility. Concomitant increases in neuronal activity within the dorsal vagal complex, including the nucleus tractus solitarius and dorsal motor nucleus of the vagus, underscore a VMH–brainstem pathway that constrains stress‐induced hypersecretory and hypermotility states. These findings delineate a central brake on vagal‐mediated gastric dysfunction and suggest potential targets for neuromodulatory interventions.

Neurobiological Mechanisms of Stress-Induced Gastric Dysfunction publication trend

The graph below shows the total number of articles in neurobiological mechanisms of stress-induced gastric dysfunction across all publications each year (not limited to Nature Index journals).

Technical terms

Restraint water‐immersion stress (RWIS): a compound stress model combining psychological restraint and partial water immersion to induce gastric injury in animal studies.

Ventromedial hypothalamic nucleus (VMH): a hypothalamic region involved in autonomic regulation of gastric function through connections to brainstem centres.

Dorsal vagal complex (DVC): a medullary centre comprising the nucleus tractus solitarius and dorsal motor nucleus of the vagus that integrates visceral sensory and motor signals to the stomach.

c‐Fos expression: a marker of neuronal activation detected by the immediate early gene protein Fos to map engaged brain regions under stress.

Astrocyte: a glial cell type that modulates synaptic activity and inflammatory responses within central autonomic nuclei.

ERK1/2 signalling pathway: an intracellular kinase cascade that transduces extracellular stress signals to neuronal and glial responses.

Central nucleus of the amygdala (CEA): a limbic structure that orchestrates autonomic and behavioural responses to stress, affecting gastric physiology.

References

1. Hypothalamic Astrocytes Respond to Gastric Mucosal Damage Induced by Restraint Water-Immersion Stress in Rat. Frontiers in Behavioral Neuroscience (2016).
2. Ventromedial hypothalamic nucleus in regulation of stress-induced gastric mucosal injury in rats. Scientific Reports (2018).
3. Altered Neuronal Activity in the Central Nucleus of the Amygdala Induced by Restraint Water-Immersion Stress in Rats. Neuroscience Bulletin (2018).
4. Neurons and Astrocytes in Ventrolateral Periaqueductal Gray Contribute to Restraint Water Immersion Stress-Induced Gastric Mucosal Damage via the ERK1/2 Signaling Pathway. The International Journal of Neuropsychopharmacology (2021).