Altered expression of NUCB2/nesfatin-1 in plasma, hypothalamus and brainstem is associated with HPA axis activity and TPH expression in chronically stressed rats.
TL;DR
Preliminary correlational evidence for coordinated NUCB2/nesfatin-1 changes across peripheral and central systems under stress-induced depression is provided, suggesting NUCB2/nesfatin-1 may link neuroendocrine activity and serotonergic plasticity with the brainstem as a core site.
Abstract
Background
The anorectic peptide nesfatin-1 has been identified as a potential mood regulator. Abnormal nesfatin-1 expression has been observed in both depression animal models and clinical cohorts, but its exact role in depression pathogenesis remains unclear.
Aim
This study aimed to detect peripheral and central nesfatin-1 alterations in rats with chronic unpredictable mild stress (CUMS)-induced depressive-like behaviors, and explore their correlations with hypothalamic-pituitary-adrenal (HPA) axis activity and brainstem monoamine synthesis.
Methods
Rats were subjected to 5-week CUMS. Enzyme-linked immunosorbent assay (ELISA) quantified plasma mature nesfatin-1 peptide, and Western blot (WB) detected full-length nucleobindin 2 (NUCB2)/nesfatin-1 in the hypothalamus and brainstem. Spearman's rank correlation was performed solely within the CUMS group (n = 6); these exploratory correlational findings require cautious interpretation due to small sample size.
Results
CUMS significantly increased plasma nesfatin-1 as well as hypothalamic and brainstem NUCB2/nesfatin-1. In CUMS rats, plasma nesfatin-1 was positively correlated with corticosterone and forced swim test (FST) immobility time, and negatively correlated with sucrose preference index(SPT) and weight gain. Brainstem NUCB2/nesfatin-1 showed a positive correlation with tryptophan hydroxylase (TPH), while no significant correlation was found between hypothalamic NUCB2/nesfatin-1 and all measured parameters.
Conclusion
Chronic stress-induced nesfatin-1 elevation accompanies peripheral HPA hyperactivation and aggravated depressive-like behaviors. Brainstem NUCB2/nesfatin-1 positively correlates with TPH, suggesting NUCB2/nesfatin-1 may link neuroendocrine activity and serotonergic plasticity with the brainstem as a core site. This study provides preliminary correlational evidence for coordinated NUCB2/nesfatin-1 changes across peripheral and central systems under stress-induced depression.