细胞酸化在癫痫终止中的可能作用机制
|
摘要
癫痫尤其是癫痫持续状态(SE),是一种严重危害人类健康的常见疾病。目前对癫痫发作和维持机制研究较多,但对癫痫如何终止却知之甚少。20世纪初已发现适度的细胞酸化可减缓或抑制癫痫患者的惊厥样发作。近年来许多研究证实,细胞酸化引起癫痫发作终止的机制与抑制性和兴奋性神经递质失衡、酸敏感性离子通道开放等机制密切相关。因此,与之相关的靶向药物和治疗手段将成为探索癫痫治疗的发展方向之一。
Epilepsy,especially the status epilepticus(SE),is a kind of common disease which is seriously dangerous for people′s health.At present,many researchers are focusing on how the epilepsy seizures happen and maintain,but know little about how it stops.It was found that appropriate cell acidification played an important role in patients to slow down or inhibit epilepsy-like seizures in the early 20 th century.Recently,more and more researches have confirmed that cell acidification can induce the termination of epileptic seizure caused by disbalance of inhibitory and excitatory transmitters of nerve,opening of acid-sensing ion channels and so on.Therefore,these will likely become the new direction to explore new drugs or methods for epileptic treatment in the future.
Epilepsy,especially the status epilepticus(SE),is a kind of common disease which is seriously dangerous for people′s health.At present,many researchers are focusing on how the epilepsy seizures happen and maintain,but know little about how it stops.It was found that appropriate cell acidification played an important role in patients to slow down or inhibit epilepsy-like seizures in the early 20 th century.Recently,more and more researches have confirmed that cell acidification can induce the termination of epileptic seizure caused by disbalance of inhibitory and excitatory transmitters of nerve,opening of acid-sensing ion channels and so on.Therefore,these will likely become the new direction to explore new drugs or methods for epileptic treatment in the future.
引文
[1]Ngugi AK,Bottomley C,Fegan G,et al.Premature mortality inactive convulsive epilepsy in rural Kenya:causes and associated actors[J].Neurology,2014,82(7):582-589.
[2]Caspers H,Speckmann EJ.Cerebral p O2,p CO2and p H:changes during convulsive activity and their significance for spontaneous arrest of seizures[J].Epilepsia,1972,13:699-725.
[3]Tolner EA,Hochman DW,Hassinen P,et al.Five percent CO2is a potent,fast-acting inhalation anticonvulsant[J].Epilepsia,2011,52(1):104-114.
[4]Tyrtyshnaia AA,Lysenko LV,Madamba F,et al.Acute neuroinflammation provokes intracellular acidification in mouse hippocampus[J].J Neuroinflammation,2016,13(1):283-293.
[5]Lennox WG.The effect on epileptic seizures of varying the composition of the respired air[J].J Clin Invest,1929,4:23-24.
[6]Gonzalez MI,Brooks-Kayal A.Altered GABA(A)receptor expression during epileptogenesis[J].Neurosci Lett,2011,497:218-222.
[7]Lado FA,MoshéSL.How do seizures stop[J].Epilepsia,2008,49(10):1651-1664.
[8]Chen Q,Armstrong D,Patrick JW,et al.Differential roles of NR2A-and NR2B-containing NMDA receptors in activity-dependent brain-derived neurotrophic factor gene regulation and limbic epileptogenesis[J].J Neurosci,2007,27(3):542-552.
[9]Fitzgerald PJ.The NMDA receptor may participate in widespread suppression of circuit level neural activity,in addition to a similarly prominent role in circuit level activation[J].Behav Brain Res,2012,230(1):291-298.
[10]Dietrich CJ,Morad M.Synaptic acidification enhances GABAA signaling[J].J Neurosci,2010,30(47):16044-16052.
[11]Tang CM,Dichter M,Morad M.Modulation of the N-methyl-Daspartate channel by extracellular H+[J].Proc Natl Acad Sci,1990,87(16):6445-6449.
[12]Benarroch EE.Acid-sensing cation channels structure,function,and pathophysiologic implications[J].Neurology,2014,82(7):628-635.
[13]Yang F,Sun X,Ding Y,et al.Astrocytic acid-sensing ion channel 1a contributes to the devolopment of chronic epileptogenesis[J].Sci Rep,2016,6:31581.
[14]Benson CJ,Xie J,Wemmie JA,et al.Heteromultimers of DEG/ENa C subunits form H+-gated channels in mouse sensory neurons[J].Proc Natl Acad Sci,2002,99(4):2338-2343.
[15]Ziemann AE,Schnizler MK,Albert GW,et al.Seizure termination by acidosis depends on ASIC1a[J].Nat Neurosci,2008,11(7):816-822.
[16]Liu S,Chen XY,Wang F,et al.Acid-sensing ion channels:potential therapeutic targets for neurologic diseases[J].Transl Neurodegener,2015,4(1):10.
[17]Wu H,Wang C,Liu B,et al.Altered expression pattern of acidsensing ion channel isoforms in piriform cortex after seizures[J].Mol Neurobiol,2016,53(3):1782-1793.
[18]Ievglevskyi O,Isaev D,Netsyk O,et al.Acid-sensing ion channels regulate spontaneous inhibitory activity in the hippocampus:possible implications for epilepsy[J].Phil Trans R Soc B,2016,371(1700):20150431.
[19]Biagini G,Babinski K,Avoli M,et al.Regional and subunitspecific downregulation of acid-sensing ion channels in the pilocarpine model of epilepsy[J].Neurobiol Dis,2001,8(1):45-58.
[20]N′Gouemo P.Amiloride delays the onset of pilocarpine-induced seizures in rats[J].Brain Res,2008,1222:230-232.
[21]Zhang HT,Gao GD,Zhang Y,et al.Glucose deficiency elevates acid-sensing ion channel 2a expression and increases seizure susceptibility in temporal lobe epilepsy[J].Sci Rep,2017,7(1):5870.
[22]Sun Z,Zhong XL,Zong Y,et al.Activation of adenosine receptor potentiates the anticonvulsant effect of phenytoin against amygdala kindled seizures[J].CNS Neurol Disord Drug Targets,2015,14(3):378-385
[23]Masino SA,Kawamura MJ,Ruskin DN.Adenosine receptors and epilepsy:current evidence and future potential[J].Int Rev Neurobiol,2014,119:233-255.
[24]Popoli P,Pepponi R.Potential therapeutic relevance of adenosine A2B and A2A receptors in the central nervous system[J].CNS Neurol Disord Drug Targets,2012,11(6):664-674.
[25]Fedele DE,Li T,Lan JQ,et al.Adenoosine A1 receptors are crucial in keeping an epileptic focus localized[J].Exp Neurol,2006,200(1):184-190.
[26]Theofilas P,Brar S,Stewart KA,et al.Adenosine kinase as a target for therapeutic antisense strategies in epilepsy[J].Epilepsia,2011,52(3):589-601.
[27]Kalappa BI,Soh H,Duignan KM,et al.Potent KCNQ2/3-specific channel activator suppresses in vivo epileptic activity and prevents the development of tinnitus[J].J Neurosci,2015,35(23):8829-8842.
[28]Jones RT,Faas GC,Mody I.Intracellular bicarbonate regulates action potential generation via KCNQ channel modulation[J].J Neurosci,2014,34(12):4409-4417.
[29]Ievglevskyi O,Isaev D,Netsyk O,et al.Acid-sensing ion channels regulate spontaneous inhibitory activity in the hippocampus:possible implications for epilepsy[J].Philos Trans R Soc B,2015,371(1700):431-439.
[30]Wojtowicz T,Wyrembek P,Lebida K,et al.Flurazepam effect on GABAergic currents depends on extracellular p H[J].Br J Pharmacol,2008,154(1):234-245.
[31]Vernier JM,Chen H,Song J.Derivatives of 5-amino-4,6-disubstituted indole and 5-amino-4,6-disubstituted indoline as potassium channel modulators:US,US8211918B2[P].2012-07-03.
[32]Vernier JM,Delarosa M,Chen H,et al.Derivatives of 4-(Nazacycloalkyl)anilides as potassium channel modulators:World Intellectual Property Organization,WO2011094186A1[P].2010-02-01.
[33]Pumain R,Ahmed MS,Kurcewicz I,et al.Lability of ABAA receptor function in human partial epilepsy:possible relationship to hypometabolism[J].Epilepsia,2008,49(8):87-90.
[34]Masino SA,Li T,Theofilas P,et al.A ketogenic diet suppresses seizures in mice through adenosine Al receptors[J].J Clin Invest,2011,121(7):2679-2683.
[2]Caspers H,Speckmann EJ.Cerebral p O2,p CO2and p H:changes during convulsive activity and their significance for spontaneous arrest of seizures[J].Epilepsia,1972,13:699-725.
[3]Tolner EA,Hochman DW,Hassinen P,et al.Five percent CO2is a potent,fast-acting inhalation anticonvulsant[J].Epilepsia,2011,52(1):104-114.
[4]Tyrtyshnaia AA,Lysenko LV,Madamba F,et al.Acute neuroinflammation provokes intracellular acidification in mouse hippocampus[J].J Neuroinflammation,2016,13(1):283-293.
[5]Lennox WG.The effect on epileptic seizures of varying the composition of the respired air[J].J Clin Invest,1929,4:23-24.
[6]Gonzalez MI,Brooks-Kayal A.Altered GABA(A)receptor expression during epileptogenesis[J].Neurosci Lett,2011,497:218-222.
[7]Lado FA,MoshéSL.How do seizures stop[J].Epilepsia,2008,49(10):1651-1664.
[8]Chen Q,Armstrong D,Patrick JW,et al.Differential roles of NR2A-and NR2B-containing NMDA receptors in activity-dependent brain-derived neurotrophic factor gene regulation and limbic epileptogenesis[J].J Neurosci,2007,27(3):542-552.
[9]Fitzgerald PJ.The NMDA receptor may participate in widespread suppression of circuit level neural activity,in addition to a similarly prominent role in circuit level activation[J].Behav Brain Res,2012,230(1):291-298.
[10]Dietrich CJ,Morad M.Synaptic acidification enhances GABAA signaling[J].J Neurosci,2010,30(47):16044-16052.
[11]Tang CM,Dichter M,Morad M.Modulation of the N-methyl-Daspartate channel by extracellular H+[J].Proc Natl Acad Sci,1990,87(16):6445-6449.
[12]Benarroch EE.Acid-sensing cation channels structure,function,and pathophysiologic implications[J].Neurology,2014,82(7):628-635.
[13]Yang F,Sun X,Ding Y,et al.Astrocytic acid-sensing ion channel 1a contributes to the devolopment of chronic epileptogenesis[J].Sci Rep,2016,6:31581.
[14]Benson CJ,Xie J,Wemmie JA,et al.Heteromultimers of DEG/ENa C subunits form H+-gated channels in mouse sensory neurons[J].Proc Natl Acad Sci,2002,99(4):2338-2343.
[15]Ziemann AE,Schnizler MK,Albert GW,et al.Seizure termination by acidosis depends on ASIC1a[J].Nat Neurosci,2008,11(7):816-822.
[16]Liu S,Chen XY,Wang F,et al.Acid-sensing ion channels:potential therapeutic targets for neurologic diseases[J].Transl Neurodegener,2015,4(1):10.
[17]Wu H,Wang C,Liu B,et al.Altered expression pattern of acidsensing ion channel isoforms in piriform cortex after seizures[J].Mol Neurobiol,2016,53(3):1782-1793.
[18]Ievglevskyi O,Isaev D,Netsyk O,et al.Acid-sensing ion channels regulate spontaneous inhibitory activity in the hippocampus:possible implications for epilepsy[J].Phil Trans R Soc B,2016,371(1700):20150431.
[19]Biagini G,Babinski K,Avoli M,et al.Regional and subunitspecific downregulation of acid-sensing ion channels in the pilocarpine model of epilepsy[J].Neurobiol Dis,2001,8(1):45-58.
[20]N′Gouemo P.Amiloride delays the onset of pilocarpine-induced seizures in rats[J].Brain Res,2008,1222:230-232.
[21]Zhang HT,Gao GD,Zhang Y,et al.Glucose deficiency elevates acid-sensing ion channel 2a expression and increases seizure susceptibility in temporal lobe epilepsy[J].Sci Rep,2017,7(1):5870.
[22]Sun Z,Zhong XL,Zong Y,et al.Activation of adenosine receptor potentiates the anticonvulsant effect of phenytoin against amygdala kindled seizures[J].CNS Neurol Disord Drug Targets,2015,14(3):378-385
[23]Masino SA,Kawamura MJ,Ruskin DN.Adenosine receptors and epilepsy:current evidence and future potential[J].Int Rev Neurobiol,2014,119:233-255.
[24]Popoli P,Pepponi R.Potential therapeutic relevance of adenosine A2B and A2A receptors in the central nervous system[J].CNS Neurol Disord Drug Targets,2012,11(6):664-674.
[25]Fedele DE,Li T,Lan JQ,et al.Adenoosine A1 receptors are crucial in keeping an epileptic focus localized[J].Exp Neurol,2006,200(1):184-190.
[26]Theofilas P,Brar S,Stewart KA,et al.Adenosine kinase as a target for therapeutic antisense strategies in epilepsy[J].Epilepsia,2011,52(3):589-601.
[27]Kalappa BI,Soh H,Duignan KM,et al.Potent KCNQ2/3-specific channel activator suppresses in vivo epileptic activity and prevents the development of tinnitus[J].J Neurosci,2015,35(23):8829-8842.
[28]Jones RT,Faas GC,Mody I.Intracellular bicarbonate regulates action potential generation via KCNQ channel modulation[J].J Neurosci,2014,34(12):4409-4417.
[29]Ievglevskyi O,Isaev D,Netsyk O,et al.Acid-sensing ion channels regulate spontaneous inhibitory activity in the hippocampus:possible implications for epilepsy[J].Philos Trans R Soc B,2015,371(1700):431-439.
[30]Wojtowicz T,Wyrembek P,Lebida K,et al.Flurazepam effect on GABAergic currents depends on extracellular p H[J].Br J Pharmacol,2008,154(1):234-245.
[31]Vernier JM,Chen H,Song J.Derivatives of 5-amino-4,6-disubstituted indole and 5-amino-4,6-disubstituted indoline as potassium channel modulators:US,US8211918B2[P].2012-07-03.
[32]Vernier JM,Delarosa M,Chen H,et al.Derivatives of 4-(Nazacycloalkyl)anilides as potassium channel modulators:World Intellectual Property Organization,WO2011094186A1[P].2010-02-01.
[33]Pumain R,Ahmed MS,Kurcewicz I,et al.Lability of ABAA receptor function in human partial epilepsy:possible relationship to hypometabolism[J].Epilepsia,2008,49(8):87-90.
[34]Masino SA,Li T,Theofilas P,et al.A ketogenic diet suppresses seizures in mice through adenosine Al receptors[J].J Clin Invest,2011,121(7):2679-2683.