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Abstract
Chronic unpredictable mild stress (CUMS) is associated with neuroendocrine dysregulation, metabolic dysfunction, immune activation, and synaptic impairment.
- Chronic stress leads to persistent stimulation of the hypothalamic-pituitary adrenal (HPA) axis, resulting in hypercortisolaemia.
- Hypercortisolaemia may contribute to insulin resistance and compromised neuroplasticity through disrupted BDNF-TrkB signaling.
- Stress can induce microbial dysbiosis and intestinal barrier disruption, which amplify central inflammation via altered tryptophan metabolism.
- Epigenetic modifications, including DNA methylation and histone remodeling, may encode changes in gene expression linked to behavioral and cognitive deficits.
- While the CUMS model has strong validity for studying stress-related disorders, its translational relevance is limited by protocol constraints.
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