Cellular and behavioral effects of lipopolysaccharide treatment are dependent upon neurokinin-1 receptor activation.
Cellular and behavioral effects of lipopolysaccharide treatment are dependent upon neurokinin-1 receptor activation.
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DOI：
10.1186/s12974-018-1098-4
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发表时间：
2018-02-27
影响因子：
9.3
通讯作者：
Schank JR
中科院分区：
文献类型：
--
作者：
Fulenwider HD;Smith BM;Nichenko AS;Carpenter JM;Nennig SE;Cheng K;Rice KC;Schank JR
一些精神疾病受到神经炎症和神经免疫激活的影响。活化B细胞的转录因子核因子kappa轻链增强子（NFkB）在炎症和先天免疫中起重要作用。神经激肽-1受体（NK1R）是神经活性肽物质P的主要内源性靶点，一些数据表明NK1R的刺激可能会影响NFkB的活性。NK1R和NFkB已被证明在复杂行为中发挥功能作用，包括应激反应、抑郁和成瘾。在本研究中，我们测试了脑内NFkB活性（由脂多糖刺激）是否依赖于NK1R。成年雄性Wistar大鼠全身注射NK1R拮抗剂L822429，然后给予全身脂多糖（LPS，一种强激活NFkB的物质）。海马提取物用于评估促炎细胞因子的表达和nfkb - dna结合电位。在行为学研究中，大鼠被训练在连续访问两瓶选择模型中消耗1% （w/v）的蔗糖溶液。在建立基线后，用L822429处理动物，并在处理后12 h测量LPS和蔗糖偏好。全身性LPS处理导致海马内促炎细胞因子表达和nfkb - dna结合活性显著增加。这些增加可通过NK1R拮抗剂L822429的系统预处理而减弱。系统性LPS治疗也会导致快感缺乏样行为的发生，蔗糖偏好测试中的蔗糖摄入量减少就是证据。用NK1R拮抗剂L822429系统预处理后，这种行为显著减弱。全身性LPS处理诱导NFkB活性显著增加，这可以通过NFkB- dna结合增加和海马中促炎细胞因子表达增加来证明。LPS也诱导了快感缺乏样行为。LPS处理的分子和行为效应都被全身NK1R拮抗显著减弱，这表明NK1R刺激位于全身LPS处理后NFkB激活的上游，并且至少在一定程度上负责NFkB激活。
Several psychiatric conditions are affected by neuroinflammation and neuroimmune activation. The transcription factor nuclear factor kappa light-chain-enhancer of activated B cells (NFkB) plays a major role in inflammation and innate immunity. The neurokinin-1 receptor (NK1R) is the primary endogenous target of the neuroactive peptide substance P, and some data suggests that NK1R stimulation may influence NFkB activity. Both NK1R and NFkB have been shown to play a functional role in complex behaviors including stress responsivity, depression, and addiction. In this study, we test whether NFkB activity in the brain (stimulated by lipopolysaccharide administration) is dependent upon the NK1R. Adult male Wistar rats were treated systemically with the NK1R antagonist L822429 followed by administration of systemic lipopolysaccharide (LPS, a strong activator of NFkB). Hippocampal extracts were used to assess expression of proinflammatory cytokines and NFkB-DNA-binding potential. For behavioral studies, rats were trained to consume 1% (w/v) sucrose solution in a continuous access two-bottle choice model. After establishment of baseline, animals were treated with L822429 and LPS and sucrose preference was measured 12 h post-treatment. Systemic LPS treatment causes a significant increase in proinflammatory cytokine expression and NFkB-DNA-binding activity within the hippocampus. These increases are attenuated by systemic pretreatment with the NK1R antagonist L822429. Systemic LPS treatment also led to the development of anhedonic-like behavior, evidenced by decreased sucrose intake in the sucrose preference test. This behavior was significantly attenuated by systemic pretreatment with the NK1R antagonist L822429. Systemic LPS treatment induced significant increases in NFkB activity, evidenced by increased NFkB-DNA binding and by increased proinflammatory cytokine expression in the hippocampus. LPS also induced anhedonic-like behavior. Both the molecular and behavioral effects of LPS treatment were significantly attenuated by systemic NK1R antagonism, suggesting that NK1R stimulation lies upstream of NFkB activation following systemic LPS administration and is at least in part responsible for NFkB activation.
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影响因子：
5
作者：
Hutson, PH;Patel, S;Barton, CL
通讯作者：
Barton, CL
影响因子：
2.9
作者：
Reis, R. C.;Brito, H. O.;Zampronio, A. R.
通讯作者：
Zampronio, A. R.
影响因子：
3.7
作者：
Calil IL;Zarpelon AC;Guerrero AT;Alves-Filho JC;Ferreira SH;Cunha FQ;Cunha TM;Verri WA Jr
通讯作者：
Verri WA Jr
影响因子：
56.9
作者：
LOTZ, M;VAUGHAN, JH;CARSON, DA
通讯作者：
CARSON, DA
影响因子：
7.2
作者：
Oeckinghaus, Andrea;Ghosh, Sankar
通讯作者：
Ghosh, Sankar