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

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초록

Objective: Accumulating evidence suggests that inflammation plays a role in the pathophysiology of major depression. The adenosinetriphosphate (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 aninflammation-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 afteradministering the bacterial endotoxin lipopolysaccharide (LPS; 0.5 mg/kg) and the effects of BBG (50 mg/kg) on depression-likebehavior 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 singledose of LPS (0.5 mg/kg). Furthermore, BBG (50 mg/kg) significantly attenuated the increase in immobility time in the TST andFST 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.

Abstract

Objective: Accumulating evidence suggests that inflammation plays a role in the pathophysiology of major depression. The adenosinetriphosphate (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 aninflammation-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 afteradministering the bacterial endotoxin lipopolysaccharide (LPS; 0.5 mg/kg) and the effects of BBG (50 mg/kg) on depression-likebehavior 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 singledose of LPS (0.5 mg/kg). Furthermore, BBG (50 mg/kg) significantly attenuated the increase in immobility time in the TST andFST 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.

참고문헌 (44)

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