中枢组胺能神经介导异氟烷麻醉后认知功能障碍
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摘要
目的:探讨组胺能神经元是否参与异氟烷麻醉引起的认知功能障碍。方法:采用抑制性回避记忆模型研究成年雄性SD大鼠异氟烷麻醉后记忆功能变化,通过下丘脑结节乳头核(TMN)微量注射GABAA受体拮抗剂荷包牡丹碱(BMI)研究组胺能核团参与异氟烷麻醉后记忆受损的神经环路机制,免疫印迹法观察组胺能神经通路对海马BDNF表达的调节作用。结果:异氟烷麻醉导致大鼠抑制性回避测试期的步入潜伏期缩短、海马BNDF表达降低;抑制性回避训练期前给予BMI,可增加麻醉大鼠在测试期的步入潜伏期及海马BNDF的表达。结论:中枢组胺能神经环路以及受该环路支配的BDNF信号通路可能为吸入麻醉后记忆受损的机制之一。
Objective: To explore whether histaminergic system participates in memory deficits after isoflurane anesthesia.Methods: The effect of isoflurane on post-anesthesia memory was investigated in male SD rats with one-trial inhibitory avoidance model.The role of histaminergic pathway in isoflurane anesthesia induced memory deficits was explored by microinfusion of GABAA receptor antagnist bicucculline methiodide(BMI) into tuberomammillary nucleus(TMN).The expression of brain-derived neurotrophic factor(BDNF) in hippocampus was assessed by western blot.Results: The step-through latency and the expression of BDNF decreased after isoflurane anesthesia.The changes were reversed by microinfusing of BMI into TMN 10 min before one-trial inhibitory avoidance training.Conclusion: Central histaminergic system and its mediated BDNF expression in hippocampus may participate in the memory deficits after isoflurane anesthesia.
Objective: To explore whether histaminergic system participates in memory deficits after isoflurane anesthesia.Methods: The effect of isoflurane on post-anesthesia memory was investigated in male SD rats with one-trial inhibitory avoidance model.The role of histaminergic pathway in isoflurane anesthesia induced memory deficits was explored by microinfusion of GABAA receptor antagnist bicucculline methiodide(BMI) into tuberomammillary nucleus(TMN).The expression of brain-derived neurotrophic factor(BDNF) in hippocampus was assessed by western blot.Results: The step-through latency and the expression of BDNF decreased after isoflurane anesthesia.The changes were reversed by microinfusing of BMI into TMN 10 min before one-trial inhibitory avoidance training.Conclusion: Central histaminergic system and its mediated BDNF expression in hippocampus may participate in the memory deficits after isoflurane anesthesia.
引文
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[14]Luo T,Leung LS.Endogenous histaminefacilitates long-term potentiation in the hip-pocampus during walking[J].J Neurosci,2010,30:7845-7852.
[15]Xu C,Michelsen KA,Wu M,et al.Hista-mine innervation and activation of septohip-pocampal GABAergic neurones:involve-ment of local ACh release[J].J Physiol,2004,561(Pt 3):657-570.
[16]Motawaj M,Arrang JM.Ciproxifan,a his-tamine H3-receptor antagonist□/□inverseagonist,modulates methamphetamine-in-duced sensitization in mice[J].Eur J Neu-rosci,2011,33:1197-1204.
[2]Luo T,Leung LS.Involvement of tube-romamillary histaminergic neurons in isoflu-rane anesthesia[J].Anesthesiology,2011,115:36-43.
[3]Zhang Y,Xu Z,Wang H,et al.Anestheticsisoflurane and desflurane differently affectmitochondrial function,learning,and mem-ory[J].Ann Neurol,2012,71:687-698.
[4]Wu X,Lu Y,Dong Y,et al.The inhalationanesthetic isoflurane increases levels ofproinflammatory TNF-α,IL-6,and IL-1β[J].Neurobiol Aging,2012,33:1364-1378.
[5]Zhang Y,Zhen Y,Dong Y,et al.Anesthet-ic propofol attenuates the isoflurane-inducedcaspase-3activation and Aβoligomerization[J].PLoS One,2011,6:e27019.
[6]Planel E,Bretteville A,Liu L,et al.Accel-eration and persistence of neurofibrillary pa-thology in a mouse model of tauopathy fol-lowing anesthesia[J].FASEB J,2009,23:2595-2604.
[7]Saab BJ,Maclean AJ,Kanisek M,et al.Short-term memory impairment after isoflu-rane in mice is prevented by theα5γ-aminobutyric acid type A receptor inverseagonist L-655,708[J].Anesthesiology,2010,113:1061-1071.
[8]Nelson LE,Guo TZ,Lu J,et al.The seda-tive component of anesthesia is mediated byGABA(A)receptors in an endogenous sleeppathway[J].Nat Neurosci,2002,5:979-584.
[9]Haas HL,Sergeeva OA,Selbach O.Hista-mine in the nervous system[J].PhysiolRev,2008,88:1183-1241.
[10]West AE,Greenberg ME.Neuronal activity-regulated gene transcription in synapse de-velopment and cognitive function[J].ColdSpring Harb Perspect Biol,2011,3,pii:a005744.
[11]Kramár EA,Chen LY,Lauterborn JC,etal.BDNF upregulation rescues synapticplasticity in middle-aged ovariectomized rats[J].Neurobiol Aging,2012,33:708-719.
[12]Xu F,Plummer MR,Len GW,et al.Brain-derived neurotrophic factor rapidly increasesNMDA receptor channel activity throughFyn-mediated phosphorylation[J].BrainRes,2006,1121:22-34.
[13]Messaoudi E,Ying SW,Kanhema T,et al.Brain-derived neurotrophic factor triggerstranscription-dependent,late phase long-term potentiation invivo[J].J Neurosci,2002,22:7453-7461.
[14]Luo T,Leung LS.Endogenous histaminefacilitates long-term potentiation in the hip-pocampus during walking[J].J Neurosci,2010,30:7845-7852.
[15]Xu C,Michelsen KA,Wu M,et al.Hista-mine innervation and activation of septohip-pocampal GABAergic neurones:involve-ment of local ACh release[J].J Physiol,2004,561(Pt 3):657-570.
[16]Motawaj M,Arrang JM.Ciproxifan,a his-tamine H3-receptor antagonist□/□inverseagonist,modulates methamphetamine-in-duced sensitization in mice[J].Eur J Neu-rosci,2011,33:1197-1204.