Effects of Brilliant Blue G on Serum Tumor Necrosis Factor-α Levels and Depression-like Behavior in Mice after Lipopolysaccharide Administration
2
조회
0
다운로드
3
인용
0
참고문헌
키워드
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)
- Dantzer R, "From inflammation to sickness and depression: when the immune system subjugates the brain", Nat Rev Neurosci, 9, pp.46~56 (2008)
- Miller AH, "Inflammation and its discontents: the role of cytokines in the pathophysiology of major depression", Biol Psychiatry, 65, pp.732~741 (2009)
- Hashimoto K., "Emerging role of glutamate in the pathophysiology of major depressive disorder", Brain Res Rev, 61, pp.105~123 (2009)
- Raison CL, "Inflammation, sanitation, and consternation: loss of contact with coevolved, tolerogenic microorganisms and the pathophysiology and treatment of major depression", Arch Gen Psychiatry, 67, pp.1211~1224 (2010)
- O'Connor JC, "Lipopolysaccharide-induced depressive-like behavior is mediated by indoleamine 2,3-dioxygenase activation in mice", Mol Psychiatry, 14, pp.511~522 (2009)
- Ohgi Y, "Effects of antidepressants on alternations in serum cytokines and depressive-like behavior in mice after lipopolysaccharide administration", Pharmacol Biochem Behav, 103, pp.853~859 (2013)
- Dowlati Y, "A meta-analysis of cytokines in major depression", Biol Psychiatry, 67, pp.446~457 (2010)
- Shelton RC, "Altered expression of genes involved in inflammation and apoptosis in frontal cortex in major depression", Mol Psychiatry, 16, pp.751~762 (2011)
- Khakh BS, "P2X receptors as cell-surface ATP sensors in health and disease", Nature, 442, pp.527~532 (2006)
- Khakh BS, "Neuromodulation by extracellular ATP and P2X receptors in the CNS", Neuron, 76, pp.51~69 (2012)
- Ferrari D, "The P2X7 receptor: a key player in IL-1processing and release", J Immunol, 176, pp.3877~3883 (2006)
- Ferrari D, "Mouse microglial cells express a plasma membrane pore gated by extracellular ATP", J Immunol, 156, pp.1531~1539 (1996)
- Ballerini P, "Rat astroglial P2Z (P2X7) receptors regulate intracellular calcium and purine release", Neuroreport, 7, pp.2533~2537 (1996)
- Matute C, "P2X(7) receptor blockade prevents ATP excitotoxicity in oligodendrocytes and ameliorates experimental autoimmune encephalomyelitis", J Neurosci, 27, pp.9525~9533 (2007)
- Deuchars SA, "Neuronal P2X7 receptors are targeted to presynaptic terminals in the central and peripheral nervous systems", J Neurosci, 21, pp.7143~7152 (2001)
- Basso AM, "Behavioral profile of P2X7 receptor knockout mice in animal models of depression and anxiety:relevance for neuropsychiatric disorders", Behav Brain Res, 198, pp.83~90 (2009)
- Csölle C, "The absence of P2X7 receptors (P2rx7)on non-haematopoietic cells leads to selective alteration in mood-related behaviour with dysregulated gene expression and stress reactivity in mice", Int J Neuropsychopharmacol, 16, pp.213~233 (2013)
- Skaper SD, "The P2X7 purinergic receptor: from physiology to neurological disorders", FASEB J, 24, pp.337~345 (2010)
- Furuyashiki T., "Roles of dopamine and inflammation-related molecules in behavioral alterations caused by repeated stress", J Pharmacol Sci, 120, pp.63~69 (2012)
- Jiang LH, "Brilliant blue G selectively blocks ATP-gated rat P2X(7) receptors", Mol Pharmacol, 58, pp.82~88 (2000)
- Jo S, "Inhibition of neuronal voltage-gated sodium channels by brilliant blue G", Mol Pharmacol, 80, pp.247~257 (2011)
- Peng W, "Systemic administration of an antagonist of the ATPsensitive receptor P2X7 improves recovery after spinal cord injury", Proc Natl Acad Sci U S A, 106, pp.12489~12493 (2009)
- Cryan JF, "The ascent of mouse: advances in modelling human depression and anxiety", Nat Rev Drug Discov, 4, pp.775~790 (2005)
- Ma XC, "Social isolation-induced aggression potentiates anxiety and depressive-like behavior in male mice subjected to unpredictable chronic mild stress", PLoS One, pp.e20955~ (2011)
- Ma XC, "Long-lasting antidepressant action of ketamine, but not glycogen synthase kinase-3 inhibitor SB216763, in the chronic mild stress model of mice", PLoS One, pp.e56053~ (2013)
- Pereira VS, "Antidepressant- and anticompulsive-like effects of purinergic receptor blockade: Involvement of nitric oxide" (2013), Eur Neuropsychopharmacol
- Boucher AA, "Resilience and reduced c-Fos expression in P2X7 receptor knockout mice exposed to repeated forced swim test", Neuroscience, 189, pp.170~177 (2011)
- Beumer W, "The immune theory of psychiatric diseases: a key role for activated microglia and circulating monocytes", J Leukoc Biol, 92, pp.959~975 (2012)
- Choi HB, "Modulation of the purinergic P2X7 receptor attenuates lipopolysaccharidemediated microglial activation and neuronal damage in inflamed brain", J Neurosci, 27, pp.4957~4968 (2007)
- Monif M, "Microglia: proliferation and activation driven by the P2X7 receptor", Int J Biochem Cell Biol, 42, pp.1753~1756 (2010)
- Clark AK, "P2X7-dependent release of interleukin-1beta and nociception in the spinal cord following lipopolysaccharide", J Neurosci, 30, pp.573~582 (2010)
- Mingam R, "In vitro and in vivo evidence for a role of the P2X7 receptor in the release of IL-1 beta in the murine brain", Brain Behav Immun, 22, pp.234~244 (2008)
- Csölle C, "Peripheral origin of IL-1beta production in the rodent hippocampus under in vivo systemic bacterial lipopolysaccharide (LPS) challenge and its regulation by P2X(7) receptors", J Neuroimmunol, 219, pp.38~46 (2010)
- Serretti A, "The genetics of bipolar disorder:genome ‘hot regions,' genes, new potential candidates and future directions", Mol Psychiatry, 13, pp.742~771 (2008)
- McGuffin P, "Whole genome linkage scan of recurrent depressive disorder from the depression network study", Hum Mol Genet, 14, pp.3337~3345 (2005)
- Kremeyer B, "Genome-wide linkage scan of bipolar disorder in a Colombian population isolate replicates Loci on chromosomes 7p21-22, 1p31, 16p12 and 21q21-22 and identifies a novel locus on chromosome 12q", Hum Hered, 70, pp.255~268 (2010)
- Lucae S, "P2RX7, a gene coding for a purinergic ligand-gated ion channel, is associated with major depressive disorder", Hum Mol Genet, 15, pp.2438~2445 (2006)
- Barden N, "Analysis of single nucleotide polymorphisms in genes in the chromosome 12Q24.31 region points to P2RX7 as a susceptibility gene to bipolar affective disorder", Am J Med Genet B Neuropsychiatr Genet, 141B, pp.374~382 (2006)
- Green EK, "P2RX7: A bipolar and unipolar disorder candidate susceptibility gene?", Am J Med Genet B Neuropsychiatr Genet, 150B, pp.1063~1069 (2009)
- Hejjas K, "Association between depression and the Gln460Arg polymorphism of P2RX7 gene: a dimensional approach", Am J Med Genet B Neuropsychiatr Genet, 150B, pp.295~299 (2009)
- McQuillin A, "Case-control studies show that a nonconservative amino-acid change from a glutamine to arginine in the P2RX7 purinergic receptor protein is associated with both bipolar- and unipolar-affective disorders", Mol Psychiatry, 14, pp.614~620 (2009)
- Grigoroiu-Serbanescu M, "Variation in P2RX7candidate gene (rs2230912) is not associated with bipolar I disorder and unipolar major depression in four European samples", Am J Med Genet B Neuropsychiatr Genet, 150B, pp.1017~1021 (2009)
- Lavebratt C, "Variations in FKBP5 and BDNF genes are suggestively associated with depression in a Swedish population-based cohort", J Affect Disord, 125, pp.249~255 (2010)
- Halmai Z, "Associations between depression severity and purinergic receptor P2RX7 gene polymorphisms", J Affect Disord, 150, pp.104~109 (2013)
