Role of P2X7 Receptor in an Animal Model of Mania Induced by D-Amphetamine
Role of P2X7 Receptor in an Animal Model of Mania Induced by D-Amphetamine
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DOI：
10.1007/s12035-014-9031-z
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发表时间：
2016-01-01
影响因子：
5.1
通讯作者：
Oliveira Battastini, Ana Maria
中科院分区：
文献类型：
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作者：
Gubert, Carolina;Fries, Gabriel Rodrigo;Oliveira Battastini, Ana Maria
本研究的目的是探讨P2 X7嘌呤能受体（P2 X7 R）和神经炎症之间的关联使用急性双相躁狂症的临床前模型。我们分析了P2 X7 R激动剂的调节作用，（3 ′-O-（4-苯甲酰基）苯甲酰基-腺苷5 ′-三磷酸，BzATP）和拮抗剂（亮蓝，BBG和3-[[5-（2，3-二氯苯基）-1H-四唑-1-基]甲基]吡啶盐酸盐，A438079）对行为相关评估的影响（自发活动）、神经炎症（白细胞介素-1 β，IL-1 β;肿瘤坏死因子α，TNF-α;和白细胞介素-6（IL-6）、氧化应激（硫代巴比妥酸反应物质，TBARS）和神经可塑性在小鼠中通过用D-苯丙胺（AMPH）（2 mg/kg）急性和慢性治疗诱导的躁狂症的药理学模型中，观察脑源性神经营养因子（BDNF）标志物。在具有阻断的P2 X7 R或在敲除（P2 X7 R（-/-））小鼠中具有P2 X7 R基因缺失的动物中观察到对AMPH的明显缺乏反应性的自发活动。同样，P2 X7 R参与AMPH诱导的促炎性和兴奋性毒性环境的增加，如通过P2 X7 R阻断引起的IL-1 β、TNF-α和TBARS水平的逆转所证明的。我们的研究结果支持这一假设，即P2 X7 R在临床前躁狂模型中由AMPH诱导的神经炎症中起作用，这可以解释行为改变。目前的数据表明，P2 X7 R可能是一个治疗的目标，有关的神经炎症报道在双相情感障碍。
The objective of this study was to explore the association between the P2X7 purinergic receptor (P2X7R) and neuroinflammation using a preclinical model of acute bipolar mania. We analyzed the modulatory effects of P2X7R agonist (3'-O-(4-benzoyl)benzoyl-adenosine 5'-triphosphate, BzATP) and antagonists (brilliant blue, BBG and 3-[[5-(2,3 dichlorophenyl)-1H-tetrazol-1-yl]methyl]pyridine hydrochloride, A438079) on assessments related to behavior (locomotor activity), neuroinflammation (interleukin-1 beta, IL-1 beta; tumor necrosis factor alpha, TNF-alpha; and interleukin- 6, IL-6), oxidative stress (thiobarbituric acid reactive substances, TBARS) and neuroplasticity (brain-derived neurotrophic factor, BDNF) markers in a pharmacological model of mania induced by acute and chronic treatment with D-amphetamine (AMPH) (2 mg/kg) in mice. An apparent lack of responsiveness to AMPH was observed in terms of the locomotor activity in animals with blocked P2X7R or with genetic deletion of P2X7R in knockout (P2X7R(-/-)) mice. Likewise, P2X7R participated in the AMPH-induced increase of the proinflammatory and excitotoxic environment, as demonstrated by the reversal of IL-1 beta, TNF-alpha, and TBARS levels caused by P2X7R blocking. Our results support the hypothesis that P2X7R plays a role in the neuroinflammation induced by AMPH in a preclinical model of mania, which could explain the altered behavior. The present data suggest that P2X7R may be a therapeutic target related to the neuroinflammation reported in bipolar disorder.