Serum Phosphorylated Irs-1 at Ser307 As a Potential Biomarker of Stress-Induced Depressive-Like Behavior in Rats Publisher Pubmed



Ghafori SS ; Mahakizadeh S ; Farahmandfar M ; Zahmatkesh M ; Nasehi M ; Bakhtiyari E ; Amini M ; Hassanzadeh G
Source: Brain Research Published:2026

Abstract

Accumulating evidence suggests that inflammation mediates stress-induced depression. Elevated pro-inflammatory cytokines may affect serum phosphorylated insulin receptor substrate-1 (phospho-IRS-1) levels. This study evaluated phospho-IRS-1 at Ser307 as a potential biomarker associated with stress-induced depressive-like behaviors. Male Wistar rats were assigned to four groups: (1) control (unstressed, ad libitum access); (2) sham (6 h/day food and water deprivation only); (3) RS14 (6 h/day restraint stress (RS) with concurrent food/water deprivation for 14 days, then stress-free until the end of the experiment); and (4) RS28 (6 h/day RS with food/water deprivation for 28 days). On day 15, serum corticosterone, IL-1β, TNF-α, and phospho-IRS-1 at Ser307 were measured, and depressive-like behaviors were assessed using FST and TST. Hippocampal histology was performed on days 15 and 30 using Nissl staining. On day 30, serum IL-1β, TNF-α, and phospho-IRS-1 at Ser307 were quantified, and behavioral assessments were conducted using FST and TST. On day 15, corticosterone, IL-1β, and TNF-α were significantly elevated in RS14 and RS28 vs. control/sham (P < 0.05), while phospho-IRS-1 at Ser307 and FST/TST outcomes showed no differences. On both days 15 and 30, the percentage of pyknotic neurons in RS14 and RS28 was higher than in control/sham, and on day 30, RS28 showed a further significant increase compared with RS14. On day 30, RS14 exhibited elevated IL-1β and TNF-α vs. control/sham, but phospho-IRS-1 at Ser307 and depressive-like behaviors were not significantly changed. In contrast, RS28 showed further increases in IL-1β, TNF-α, and phospho-IRS-1 at Ser307, along with altered FST (swimming, climbing, immobility times) and TST (immobility latency/time) parameters compared with all other groups (P < 0.05). These findings suggest that increased serum phospho-IRS-1 at Ser307 may serve as a biomarker for stress-induced depressive-like behaviors. © 2025