Tuberoinfundibular Peptide of 39 Attenuates Chronic Unpredictable Mild Stress Induced HPA Axis Dysregulation, Inflammation and Oxidative Damage in Depressive Rats

Background: Tuberoinfundibular Peptide of 39 (TIP39) is a neuroendocrine hormone, potentially acting through parathyroid hormone receptor 2 receptor (PTH2R) abundantly expressed in brain. Objective: This study aimed to evaluate the neuroendocrine role of TIP39 in chronic unpredictable mild stress (CUMS) induced depression and to elucidate its underlying mechanism. Method: The depression was induced in rats by CUMS for a period of four weeks. TIP39 was administered through intracerebroventricular (ICV) route at doses (1 & 10 nmol/rat) for four weeks on alternate days, parallel with the daily exposure of stress. At the end of the treatment period, animals were evaluated for sucrose preference, behavioral, biochemical and oxidative changes. Further the molecular mechanism of anti-stress activity of TIP39 confirmed through gene expression study. Results: TIP39 administration significantly reversed the CUMS induced increased immobility time in depressive rats and increased plasma corticosterone as well as decreased open-field activity and sucrose consumption. CUMS lowers the activity of superoxide dismutase (SOD), catalase (CAT) and glutathione (GSH) and elevated the production of malondialdehyde (MDA) in hippocampus and prefrontal cortex, which was reversed by the administration of TIP39. Moreover, TIP39 could effectively reverse alteration in interleukin 6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in brain tissue. Conclusion: Chronic ICV administration of TIP39 alleviated the behavioral deficits of chronic unpredictable mild stress, consanguinity to its concurrent modulatory repercussion on hypothalamic pituitary adrenal axis, inflammation, and oxidative courses.