Suramin protects against chronic stress-induced neurobehavioral deficits via cGAS–STING/NF-κB suppression

Prolonged exposure to stress alters brain pathophysiology by increasing inflammation leading to cellular and molecular dysfunction and initiation of neurobehavioral changes like anxiety, depression and cognitive impairment. Various signaling pathways and downstream cascades modulate the inflammatory responses within the Central Nervous System (CNS), notably cGAS-STING pathway and Nuclear factor kappa B (NF-κB) signaling are majorly affected. The present research aims to assess the consequence of modulation of cGAS with suramin in chronic unpredictable stress (CUS), and examining the impact on neurobehavioral alterations. For evaluating the impact of CUS and pharmacological interventions on neurobehavioral changes, Swiss albino mice of either sex were exposed to various stressors for 8 weeks. The behavioral traits for anxiety, depression and memory impairment were assessed by Elevated Plus Maze (EPM), Forced Swim Test (FST), Sucrose Preference Test (SPT), Tail Suspension Test (TST), Morris Water Maze (MWM) and Passive Avoidance Test (PAT). The level of corticosterone and neurotransmitters (dopamine and serotonin); various parameters of oxidative stress and neuroinflammation; acetylcholinesterase (AChE) activity and histological changes in hippocampus and cortex were also assessed. The results highlighted that administration of suramin (5, 10 and 20 mg/kg, i.p.) dose dependently improves neurobehavioral parameters, decreases corticosterone; elevates the level of neurotransmitters, and reduces the deleterious effects of CUS on oxidative stress and neuroinflammation; along with the histological improvement by inhibiting the cGAS-STING pathway and modulating NF-κB signaling as observed from decrease NF-κB levels in our study This study provides insights into suramin as a new treatment approach for mitigating the effects of chronic stress on restoring neurobehavioral changes.