Effects of Brilliant Blue G on Serum Tumor Necrosis Factor-α Levels and Depression-like Behavior in Mice after Lipopolysaccharide Administration

Abstract

Objective: Accumulating evidence suggests that inflammation plays a role in the pathophysiology of major depression. The adenosine triphosphate (ATP)-sensitive P2X7 receptor (P2X7R) plays a crucial role in microglial activation caused by inflammation. The dye brilliant blue G (BBG) is a P2X7R antagonist. This study examined whether BBG shows antidepressant effects in an inflammation-induced model of depression.

Methods: We examined the effects of BBG (12.5, 25, or 50 mg/kg) on serum tumor necrosis factor-α (TNF-α) levels after administering the bacterial endotoxin lipopolysaccharide (LPS; 0.5 mg/kg) and the effects of BBG (50 mg/kg) on depression-like behavior in the tail-suspension test (TST) and forced swimming test (FST).

Results: Pretreatment with BBG (12.5, 25, or 50 mg/kg) significantly blocked the increase in serum TNF-α levels after a single dose of LPS (0.5 mg/kg). Furthermore, BBG (50 mg/kg) significantly attenuated the increase in immobility time in the TST and FST after LPS (0.5 mg/kg) administration.

Conclusion: The results suggest that BBG has anti-inflammatory and antidepressant effects in mice after LPS administration. Therefore, P2X7R antagonists are potential therapeutic drugs for inflammation-related major depression.

Keywords: Coomassie Brilliant Blue; Cytokine; Depression; Inflammation; Purinergic P2X7 receptors; Tumor necrosis factor-alpha.

Fig. 1

Effects of brilliant blue G (BBG) on the lipopolysaccharide (LPS)-induced increase in serum tumor necrosis factor-α (TNF-α) levels. Thirty minutes after a single intraperitoneally (i.p.) dose of vehicle (10 ml/kg) or BBG (12.5, 25, or 50 mg/kg), saline (10 ml/kg) or LPS (0.5 mg/kg) was injected i.p. Blood was collected 90 minutes after the LPS (or saline) injection. The serum TNF-α concentration was measured with ELISA. The bars in the figure are shown as the mean±SEM (n=8). ^*p<0.05, ^†p<0.001 compared with the LPS-treated group (black column).

Fig. 2

Antidepressant effects of brilliant blue G (BBG) on lipopolysaccharide (LPS)-induced depression-like behavior in mice. BBG (50 mg/kg) or vehicle (10 ml/kg) was administered intraperitoneally (i.p.) 30 minutes before LPS (0.5 mg/kg, i.p.) administration. Behavior was evaluated 24 hours after the LPS injection. (A) locomotion, (B) tail-suspension test (TST), (C) forced swimming test (FST). The bars in the figure are the mean±SEM (n=12-14). ^*p<0.05, ^†p<0.01 compared with the LPS-treated group (black column).