丙泊酚通过降低眶额叶皮层神经元兴奋性下调大鼠认知功能研究
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摘要
目的探讨丙泊酚对眶额叶皮层兴奋性及相关学习记忆功能的影响。方法采用神经药理学方法在眶额叶皮层微注射丙泊酚,检测大鼠在T-迷宫中的反转学习记忆功能及开场实验中运动、情绪和探索动机的变化;通过免疫组化检测c-fos表达,观测丙泊酚对眶额叶皮层神经元兴奋性的影响。结果眶额叶皮层微注射丙泊酚后,大鼠在T-迷宫中的学习记忆能力下降(P <0. 05);开场实验中眶额叶微注射丙泊酚未影响大鼠的运功、情绪及探索能力(P> 0. 05);丙泊酚可显著抑制眶额叶皮层c-fos表达。结论丙泊酚可直接抑制眶额叶皮层神经元的活动,引起学习记忆能力下调,表明眶额叶皮层是丙泊酚发挥麻醉效应的重要靶区。
Objective To investigate the effect of propofol on the excitability of orbitofrontal cortex and related learning and memory function. Methods Propofol was microinjected into the orbitofrontal cortex by means of neuropharmacology. T-maze was used to detect the reversal learning and memory function,and the open field test was used to detect the changes in animals' locomotor,emotion and exploratory activities. The expression of c-fos was detected by immunohistochemistry to observe the effect of propofol on the neuronal excitability of the orbitofrontal cortex. Results After microinjection of propofol into the orbitofrontal cortex,the learning and memory abilities of rats in T-maze decreased( P < 0. 05). Microinjection of propofol into the orbitofrontal cortex did not affect the locomotor,emotion and exploratory activities of rats in the open field test( P > 0. 05). Propofol could significantly inhibit the expression of c-fos in the orbitofrontal cortex. Conclusion Propofol can down-regulate learning and memory function via directly inhibiting the neuronal activity in the orbitofrontal cortex,which indicates that the orbitofrontal cortex is the important target for propofol to exert anesthetic effect.
Objective To investigate the effect of propofol on the excitability of orbitofrontal cortex and related learning and memory function. Methods Propofol was microinjected into the orbitofrontal cortex by means of neuropharmacology. T-maze was used to detect the reversal learning and memory function,and the open field test was used to detect the changes in animals' locomotor,emotion and exploratory activities. The expression of c-fos was detected by immunohistochemistry to observe the effect of propofol on the neuronal excitability of the orbitofrontal cortex. Results After microinjection of propofol into the orbitofrontal cortex,the learning and memory abilities of rats in T-maze decreased( P < 0. 05). Microinjection of propofol into the orbitofrontal cortex did not affect the locomotor,emotion and exploratory activities of rats in the open field test( P > 0. 05). Propofol could significantly inhibit the expression of c-fos in the orbitofrontal cortex. Conclusion Propofol can down-regulate learning and memory function via directly inhibiting the neuronal activity in the orbitofrontal cortex,which indicates that the orbitofrontal cortex is the important target for propofol to exert anesthetic effect.
引文
[1] CHOI GJ,KANG H,BAEK CW,et al. Comparison of bolus versus continuous infusion of propofol for procedural sedation:a metaanalysis[J]. Curr Med Res Opin,2017,33(11):1935-1943.
[2] FENG AY,KAYE AD,KAYE RJ,et al. Novel propofol derivatives and implications for anesthesia practice[J]. J Anaesthesiol Clin Pharmacol,2017,33(1):9-15.
[3] ILYAS M,BUTT MF,BILAL M,et al. A Review of Modern Control Strategies for Clinical Evaluation of Propofol Anesthesia Administration Employing Hypnosis Level Regulation[J]. Biomed Res Int,2017,2017:7432310.
[4] PANG R,QUARTERMAIN D,ROSMAN E,et al. Effect of propofol on memory in mice[J]. Pharmacol Biochem Behav,1993,44(1):145-151.
[5] SANOU J,ILBOUDO D,GOODALL G,et al. Evaluation of cognitive functions after anesthesia with propofol[J]. Ann Fr Anesth Reanim,1996,15(8):1155-1161.
[6] XU X,TIAN Y,WANG G,et al. Inhibition of propofol on single neuron and neuronal ensemble activity in prefrontal cortex of rats during working memory task[J]. Behav Brain Res,2014,270:270-276.
[7] KAKEHATA J,TOGASHI H,YAMAGUCHI T,et al. Effects of propofol and halothane on long-term potentiation in the rat hippocampus after transient cerebral ischaemia[J]. Eur J Anaesthesiol,2007,24(12):1021-1027.
[8] SUN X,ZHANG J,LI H,et al. Propofol effects on excitatory synaptic efficacy in the CA 1 region of the developing hippocampus[J]. Brain Res Dev Brain Res,2005,157(1):1-7.
[9] WEI HM,XIONG WY,YANG SC,et al. Propofol facilitates the development of long-term depression(LTD)and impairs the maintenance of long-term potentiation(LTP)in the CA1 region of the hippocampus of anesthetized rats[J]. Neurosci Lett,2002,324(3):181-184.
[10] KIKUCHI T,WANG Y,SATO K,et al. In vivo effects of propofol on acetylcholine release from the frontal cortex,hippocampus and striatum studied by intracerebral microdialysis in freely moving rats[J]. Br J Anaesth,1998,80(5):644-648.
[11] MATSUO M,AYUSE T,K OI,et al. Propofol produces anticonflict action by inhibiting 5-HT release in rat dorsal hippocampus[J]. Neuroreport,1997,8(14):3087-3090.
[12] LI XJ,PAN K,ZHU D,et al. Propofol postsynaptically suppresses stellate neuron excitability in the entorhinal cortex by influencing the HCN and TREK-2 channels[J]. Neurosci Lett,2016,619:54-59.
[13] WALTON ME,BEHRENS TE,BUCKLEY MJ,et al. Separable learning systems in the macaque brain and the role of orbitofrontal cortex in contingent learning[J]. Neuron,2010,65(6):927-939.
[14] MCDANNALD MA,LUCANTONIO F,BURKE KA,et al. Ventral striatum and orbitofrontal cortex are both required for modelbased,but not model-free,reinforcement learning[J]. J Neurosci,2011,31(7):2700-2705.
[15] TREMBLAY L,SCHULTZ W. Relative reward preference in primate orbitofrontal cortex[J]. Nature,1999,398(6729):704-708.
[16] PADOA-SCHIOPPA C,ASSAD JA,Neurons in the orbitofrontal cortex encode economic value[J]. Nature,2006,441(7090):223-226.
[17] FISET P,PAUS T,DALOZE T,et al. Brain mechanisms of propofol-induced loss of consciousness in humans:a positron emission tomographic study[J]. J Neurosci,1999,19(13):5506-5513.
[18] FUNAHASHI M,HIGUCHI H,MIYAWAKI T,et al. Propofol suppresses a hyperpolarization-activated inward current in rat hippocampal CA1 neurons[J]. Neurosci Lett,2001,311(3):177-180.
[19] ONGUR D,PRICE JL. The organization of networks within the orbital and medial prefrontal cortex of rats,monkeys and humans[J].Cereb Cortex,2000,10(3):206-219.
[20] WAY BM,LACAN G,FAIRBANKS LA,et al. Architectonic distribution of the serotonin transporter within the orbitofrontal cortex of the vervet monkey[J]. Neuroscience,2007,148(4):937-948.
[21] DEACON TW,EICHENBAUM H,ROSENBERG P,et al. Afferent connections of the perirhinal cortex in the rat[J]. J Comp Neurol,1983,220(2):168-190.
[22] RICEBERG JS,SHAPIRO ML. Reward stability determines the contribution of orbitofrontal cortex to adaptive behavior[J].J Neurosci,2012,32(46):16402-16409.
[23] THORPE SJ,ROLLS ET,MADDISON S. The orbitofrontal cortex:neuronal activity in the behaving monkey[J]. Exp Brain Res,1983,49(1):93-115.
[24] ROLLS ET,CRITCHLEY HD,MASON R,et al. Orbitofrontal cortex neurons:role in olfactory and visual association learning[J].J Neurophysiol,1996,75(5):1970-1981.
[25] INOUE Y,SHIBUYA I,KABASHIMA N,et al. The mechanism of inhibitory actions of propofol on rat supraoptic neurons[J].Anesthesiology,1999,91(1):167-178.
[26] REHBERG B,DUCH DS. Suppression of central nervous system sodium channels by propofol[J]. Anesthesiology,1999,91(2):512-520.
[27] HIGUCHI H,FUNAHASHI M,MIYAWAKI T,et al. Suppression of the hyperpolarization-activated inward current contributes to the inhibitory actions of propofol on rat CA1 and CA3 pyramidal neurons[J]. Neurosci Res,2003,45(4):459-472.
[2] FENG AY,KAYE AD,KAYE RJ,et al. Novel propofol derivatives and implications for anesthesia practice[J]. J Anaesthesiol Clin Pharmacol,2017,33(1):9-15.
[3] ILYAS M,BUTT MF,BILAL M,et al. A Review of Modern Control Strategies for Clinical Evaluation of Propofol Anesthesia Administration Employing Hypnosis Level Regulation[J]. Biomed Res Int,2017,2017:7432310.
[4] PANG R,QUARTERMAIN D,ROSMAN E,et al. Effect of propofol on memory in mice[J]. Pharmacol Biochem Behav,1993,44(1):145-151.
[5] SANOU J,ILBOUDO D,GOODALL G,et al. Evaluation of cognitive functions after anesthesia with propofol[J]. Ann Fr Anesth Reanim,1996,15(8):1155-1161.
[6] XU X,TIAN Y,WANG G,et al. Inhibition of propofol on single neuron and neuronal ensemble activity in prefrontal cortex of rats during working memory task[J]. Behav Brain Res,2014,270:270-276.
[7] KAKEHATA J,TOGASHI H,YAMAGUCHI T,et al. Effects of propofol and halothane on long-term potentiation in the rat hippocampus after transient cerebral ischaemia[J]. Eur J Anaesthesiol,2007,24(12):1021-1027.
[8] SUN X,ZHANG J,LI H,et al. Propofol effects on excitatory synaptic efficacy in the CA 1 region of the developing hippocampus[J]. Brain Res Dev Brain Res,2005,157(1):1-7.
[9] WEI HM,XIONG WY,YANG SC,et al. Propofol facilitates the development of long-term depression(LTD)and impairs the maintenance of long-term potentiation(LTP)in the CA1 region of the hippocampus of anesthetized rats[J]. Neurosci Lett,2002,324(3):181-184.
[10] KIKUCHI T,WANG Y,SATO K,et al. In vivo effects of propofol on acetylcholine release from the frontal cortex,hippocampus and striatum studied by intracerebral microdialysis in freely moving rats[J]. Br J Anaesth,1998,80(5):644-648.
[11] MATSUO M,AYUSE T,K OI,et al. Propofol produces anticonflict action by inhibiting 5-HT release in rat dorsal hippocampus[J]. Neuroreport,1997,8(14):3087-3090.
[12] LI XJ,PAN K,ZHU D,et al. Propofol postsynaptically suppresses stellate neuron excitability in the entorhinal cortex by influencing the HCN and TREK-2 channels[J]. Neurosci Lett,2016,619:54-59.
[13] WALTON ME,BEHRENS TE,BUCKLEY MJ,et al. Separable learning systems in the macaque brain and the role of orbitofrontal cortex in contingent learning[J]. Neuron,2010,65(6):927-939.
[14] MCDANNALD MA,LUCANTONIO F,BURKE KA,et al. Ventral striatum and orbitofrontal cortex are both required for modelbased,but not model-free,reinforcement learning[J]. J Neurosci,2011,31(7):2700-2705.
[15] TREMBLAY L,SCHULTZ W. Relative reward preference in primate orbitofrontal cortex[J]. Nature,1999,398(6729):704-708.
[16] PADOA-SCHIOPPA C,ASSAD JA,Neurons in the orbitofrontal cortex encode economic value[J]. Nature,2006,441(7090):223-226.
[17] FISET P,PAUS T,DALOZE T,et al. Brain mechanisms of propofol-induced loss of consciousness in humans:a positron emission tomographic study[J]. J Neurosci,1999,19(13):5506-5513.
[18] FUNAHASHI M,HIGUCHI H,MIYAWAKI T,et al. Propofol suppresses a hyperpolarization-activated inward current in rat hippocampal CA1 neurons[J]. Neurosci Lett,2001,311(3):177-180.
[19] ONGUR D,PRICE JL. The organization of networks within the orbital and medial prefrontal cortex of rats,monkeys and humans[J].Cereb Cortex,2000,10(3):206-219.
[20] WAY BM,LACAN G,FAIRBANKS LA,et al. Architectonic distribution of the serotonin transporter within the orbitofrontal cortex of the vervet monkey[J]. Neuroscience,2007,148(4):937-948.
[21] DEACON TW,EICHENBAUM H,ROSENBERG P,et al. Afferent connections of the perirhinal cortex in the rat[J]. J Comp Neurol,1983,220(2):168-190.
[22] RICEBERG JS,SHAPIRO ML. Reward stability determines the contribution of orbitofrontal cortex to adaptive behavior[J].J Neurosci,2012,32(46):16402-16409.
[23] THORPE SJ,ROLLS ET,MADDISON S. The orbitofrontal cortex:neuronal activity in the behaving monkey[J]. Exp Brain Res,1983,49(1):93-115.
[24] ROLLS ET,CRITCHLEY HD,MASON R,et al. Orbitofrontal cortex neurons:role in olfactory and visual association learning[J].J Neurophysiol,1996,75(5):1970-1981.
[25] INOUE Y,SHIBUYA I,KABASHIMA N,et al. The mechanism of inhibitory actions of propofol on rat supraoptic neurons[J].Anesthesiology,1999,91(1):167-178.
[26] REHBERG B,DUCH DS. Suppression of central nervous system sodium channels by propofol[J]. Anesthesiology,1999,91(2):512-520.
[27] HIGUCHI H,FUNAHASHI M,MIYAWAKI T,et al. Suppression of the hyperpolarization-activated inward current contributes to the inhibitory actions of propofol on rat CA1 and CA3 pyramidal neurons[J]. Neurosci Res,2003,45(4):459-472.