海马苔藓纤维出芽分子机制及在颞叶癫痫中的作用_Journal of Epilepsy

Authors：

 黄文立 ,  黄华品

福建医科大学协和临床医学院福建医科大学附属协和医院福建医科大学脑血管病研究所(福州，350001);

Corresponding author：

黄华品, Email: hh-p@163.com

Keywords：

海马苔藓纤维出芽; 颞叶癫痫; 细胞外信号调节激酶; 雷帕霉素靶蛋白

DOI：

10.7507/2096-0247.20160030

Video：

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Abstract Full text Figures/Tables Video References Cited by

颞叶癫痫是难治性癫痫中最常见的类型，苔藓纤维出芽(Mossy fiber sproutinggranular, MFS)是颞叶癫痫患者最特征性的病理变化，但其分子信号通路及在颞叶癫痫中的作用至今还未明确。现综述近年有关MFS的信号通路及其在颞叶癫痫中作用。首先从颗粒细胞轴突出芽相关的信号通路进行阐述，主要包括细胞外信号调节激酶通路调节神经元胞体和轴突生长发育的作用，还有雷帕霉素靶蛋白转导通路对痫性发作的影响以及调节细胞增殖、突触重塑的作用。然后进一步阐述MFS到底促进还是抑制癫痫的发生以及与颞叶癫痫的因果关系。为颞叶癫痫的发生机制及治疗提供新思路。

Citation： 黄文立, 黄华品. 海马苔藓纤维出芽分子机制及在颞叶癫痫中的作用. Journal of Epilepsy, 2016, 2(2): 155-158. doi: 10.7507/2096-0247.20160030 Copy

1.	Koyama R. Cellular and molecular mechanisms underlying aberrant network reorganization in the epileptic brain. Yakugaku zasshi: Journal of the Pharmaceutical Society of Japan, 2013, 134(11): 1171-1177.
2.	Chen LL, Feng HF, Mao XX, et al. One hour of pilocarpine-induced status epilepticus is sufficient to develop chronic epilepsy in mice, and is associated with mossy fiber sprouting but not neuronal death. Neuroscience Bulletin, 2013, 29(3): 295-302.
3.	Huang WJ, Tian FF, Chen JM, et al. GSK?3β may be involved in hippocampal mossy fiber sprouting in the pentylenetetrazole?kindling model. Molecular Medicine Reports, 2013, 8(5): 1337-1342.
4.	Dyhrfjeld-Johnsen J, Santhakumar V, Morgan RJ, et al. Topological determinants of epileptogenesis in large-scale structural and functional models of the dentate gyrus derived from experimental data. Journal of Neurophysiology, 2007, 97(2): 1566-1587.
5.	Sloviter RS, Zappone CA, Harvey BD, et al. Kainic acid‐induced recurrent mossy fiber innervation of dentate gyrus inhibitory interneurons: possible anatomical substrate of granule cell hyperinhibition in chronically epileptic rats. Journal of Comparative Neurology, 2006, 494(6): 944-960.
6.	Lin H, Huang Y, Wang Y, et al. Spatiotemporal profile of N cadherin expression in the mossy fiber sprouting and synaptic plasticity following seizures. Mol Cell Biochem, 2011, 358(45): 201 205.
7.	Thomas GM, Huganir RL. MAPK cascade signalling and synaptic plasticity. Nature Reviews Neuroscience, 2004, 5(3): 173-183.
8.	Dulla CG. More than mTOR? Novel roles for MEK-ERK1/2 and FLNA in tuberous sclerosis complex. Epilepsy Currents, 2015, 15(4): 221-222.
9.	Jiang G, Wang W, Cao Q, et al. Insulin growth factor-1 (IGF-1) enhances hippocampal excitatory and seizure activity through IGF-1 receptor-mediated mechanisms in the epileptic brain. Clinical Science, 2015, 129(12): 1047-1060.
10.	Glazova MV, Nikitina LS, Hudik KA, et al. Inhibition of ERK1/2 signaling prevents epileptiform behavior in rats prone to audiogenic seizures. Journal of Neurochemistry, 2015, 132(2): 218-229.
11.	Zu-Cai Xu, Yang-Mei Chen, Ping Xu, et al. Epileptiform Discharge Upregulates P-Erk1/2, Growth-Associated Protein 43 and Synaptophysin in Cultured Rat Hippocampal Neurons. Seizure, 2009, 18 (9): 680-685.
12.	Orlova KA, Crino PB. The tuberous sclerosis complex. Annals of the New York Academy of Sciences, 2010, 1184(1): 87-105.
13.	Goto J, Talos DM, Klein P, et al. Regulable neural progenitor-specific Tsc1 loss yields giant cells with organellar dysfunction in a model of tuberous sclerosis complex. Proceedings of the National Academy of Sciences, 2011, 108(45): E1070-E1079.
14.	Zhang L, Bartley CM, Gong X, et al. MEK-ERK1/2-dependent FLNA overexpression promotes abnormal dendritic patterning in tuberous sclerosis independent of mTOR. Neuron, 2014, 84(1): 78-91.
15.	Alhaj MW, Zaitone SA, Moustafa YM. Fluvoxamine alleviates seizure activity and downregulates hippocampal GAP-43 expression in pentylenetetrazole-kindled mice: role of 5-HT3 receptors. Behavioural Pharmacology, 2015, 26(4): 369-382.
16.	Latchney SE, Masiulis I, Zaccaria KJ, et al. Developmental and adult GAP-43 deficiency in mice dynamically alters hippocampal neurogenesis and mossy fiber volume. Developmental Neuroscience, 2014, 36(1): 44-63.
17.	Decker JM, Krüger L, Sydow A, et al. Pro-aggregant Tau impairs mossy fiber plasticity due to structural changes and Ca dysregulation. Acta Neuropathologica Communications, 2015, 1(3): 1-18.
18.	Kandratavicius L, Monteiro MR, Assirati Jr JA, et al. Neurotrophins in mesial temporal lobe epilepsy with and without psychiatric comorbidities. Journal of Neuropathology & Experimental Neurology, 2013, 72(11): 1029-1042.
19.	Xu ZC, Chen YM, Xu P, et al. Epileptiform discharge upregulates p-ERK1/2, growth-associated protein 43 and synaptophysin in cultured rat hippocampal neurons. Seizure, 2009, 18(10): 680-685.
20.	Hu B, Liu C, Bramlett H, et al. Changes in trkB-ERK1/2-CREB/Elk-1 pathways in hippocampal mossy fiber organization after traumatic brain injury. Journal of Cerebral Blood Flow & Metabolism, 2004, 24(8): 934.
21.	Shomit Sengupta, Timothy R Peterson, David M Sabatini. Regulation of the mtor complex 1 pathway by nutrients, growth factors, and stress. Molecular Cell, 2010, 40 (21): 310-322.
22.	Catherine A Vickers, Kirsten S Dickson, David JA Wyllie. Induction and maintenance of late-phase long-term potentiation in isolated dendrites of rat hippocampal ca1 pyramidal neurones. The Journal of Physiology, 2005, 568 (17): 803-813.
23.	Yunfei Huang, Bingnan N Kang, Jing Tian, et al. The Cationic Amino Acid Transporters Cat1 and Cat3 Mediate Nmda Receptor Activation-Dependent Changes in Elaboration of Neuronal Proces Via the Mammalian Target of Rapamycin Mtor Pathway. The Journal of Neuroscience, 2007, 27 (10): 449-458.
24.	Russo E, Citraro R, Donato G, et al. mTOR inhibition modulates epileptogenesis, seizures and depressive behavior in a genetic rat model of absence epilepsy. Neuropharmacology, 2013, 69(12): 25-36.
25.	Wong M. Mammalian target of rapamycin (mTOR) inhibition as a potential antiepileptogenic therapy: from tuberous sclerosis to common acquired epilepsies. Epilepsia, 2010, 51(1): 27-36.
26.	Wang SJ, Bo QY, Zhao XH, et al. Resveratrol pre-treatment reduces early inflammatory responses induced by status epilepticus via mTOR signaling. Brain Research, 2013, 1492(1): 122-129.
27.	Tang H, Long H, Zeng C, et al. Rapamycin suppresses the recurrent excitatory circuits of dentate gyrus in a mouse model of temporal lobe epilepsy. Biochemical and Biophysical Research Communications, 2012, 420(1): 199-204.
28.	Zhou J, Blundell J, Ogawa S, et al. Pharmacological inhibition of mTORC1 suppresses anatomical, cellular, and behavioral abnormalities in neural-specific Pten knock-out mice. The Journal of Neuroscience, 2009, 29(6): 1773-1783.
29.	Meikle L, Pollizzi K, Egnor A, et al. Response of a neuronal model of tuberous sclerosis to mammalian target of rapamycin (mTOR) inhibitors: effects on mTORC1 and Akt signaling lead to improved survival and function. The Journal of Neuroscience, 2008, 28(21): 5422-5432.
30.	Buckmaster PS, Ingram EA, Wen X. Inhibition of the mammalian target of rapamycin signaling pathway suppresses dentate granule cell axon sprouting in a rodent model of temporal lobe epilepsy. The Journal of Neuroscience, 2009, 29(25): 8259-8269.
31.	Ling-Hui Zeng, Nicholas R Rensing, Michael Wong. The Mammalian Target of Rapamycin Signaling Pathway Mediates Epileptogenesis in a Model of Temporal Lobe Epilepsy. The Journal of Neuroscience, 2009, 29 (20): 6964-6972.
32.	Felicia H Lew, Paul S Buckmaster. Is There a Critical Period for Mossy Fiber Sprouting in a Mouse Model of Temporal Lobe Epilepsy?. Epilepsia, 2011, 52 (11): 2326-2332.
33.	Haiyun Tang, Hongyu Long, Chang Zeng, et al. Rapamycin Suppresses the Recurrent Excitatory Circuits of Dentate Gyrus in a Mouse Model of Temporal Lobe Epilepsy. Biochemical and Biophysical Research Communications, 2012, 420 (32): 199-204.
34.	Jonas Dyhrfjeld-Johnsen, Vijayalakshmi Santhakumar, Robert J Morgan, et al. Topological Determinants of Epileptogenesis in Large-Scale Structural and Functional Models of the Dentate Gyrus Derived from Experimental Data. Journal of Neurophysiology, 2007, 97 (11): 1566-1587.
35.	Kron MM, Zhang H, Parent JM. The developmental stage of dentate granule cells dictates their contribution to seizure-induced plasticity. The Journal of Neuroscience, 2010, 30(6): 2051-2059.
36.	Lew FH, Buckmaster PS. Is there a critical period for mossy fiber sprouting in a mouse model of temporal lobe epilepsy? Epilepsia, 2011, 52(12): 2326-2332.
37.	Heng K, Haney MM, Buckmaster PS. High‐dose rapamycin blocks mossy fiber sprouting but not seizures in a mouse model of temporal lobe epilepsy. Epilepsia, 2013, 54(9): 1535-1541.
38.	Huang X, Zhang H, Yang J, et al. Pharmacological inhibition of the mammalian target of rapamycin pathway suppresses acquired epilepsy. Neurobiology of Disease, 2010, 40(1): 193-199.
39.	Zeng L-H, Rensing NR, Wong M. The mammalian target of rapamycin signaling pathway mediates epileptogenesis in a model of temporal lobe epilepsy. The Journal of Neuroscience, 2009, 29(21): 6964-6972.
40.	Sliwa A, Plucinska G, Bednarczyk J, et al. Post-treatment with rapamycin does not prevent epileptogenesis in the amygdala stimulation model of temporal lobe epilepsy. Neuroscience Letters, 2012, 509(2): 105-109.

1. Koyama R. Cellular and molecular mechanisms underlying aberrant network reorganization in the epileptic brain. Yakugaku zasshi: Journal of the Pharmaceutical Society of Japan, 2013, 134(11): 1171-1177.
2. Chen LL, Feng HF, Mao XX, et al. One hour of pilocarpine-induced status epilepticus is sufficient to develop chronic epilepsy in mice, and is associated with mossy fiber sprouting but not neuronal death. Neuroscience Bulletin, 2013, 29(3): 295-302.
3. Huang WJ, Tian FF, Chen JM, et al. GSK?3β may be involved in hippocampal mossy fiber sprouting in the pentylenetetrazole?kindling model. Molecular Medicine Reports, 2013, 8(5): 1337-1342.
4. Dyhrfjeld-Johnsen J, Santhakumar V, Morgan RJ, et al. Topological determinants of epileptogenesis in large-scale structural and functional models of the dentate gyrus derived from experimental data. Journal of Neurophysiology, 2007, 97(2): 1566-1587.
5. Sloviter RS, Zappone CA, Harvey BD, et al. Kainic acid‐induced recurrent mossy fiber innervation of dentate gyrus inhibitory interneurons: possible anatomical substrate of granule cell hyperinhibition in chronically epileptic rats. Journal of Comparative Neurology, 2006, 494(6): 944-960.
6. Lin H, Huang Y, Wang Y, et al. Spatiotemporal profile of N cadherin expression in the mossy fiber sprouting and synaptic plasticity following seizures. Mol Cell Biochem, 2011, 358(45): 201 205.
7. Thomas GM, Huganir RL. MAPK cascade signalling and synaptic plasticity. Nature Reviews Neuroscience, 2004, 5(3): 173-183.
8. Dulla CG. More than mTOR? Novel roles for MEK-ERK1/2 and FLNA in tuberous sclerosis complex. Epilepsy Currents, 2015, 15(4): 221-222.
9. Jiang G, Wang W, Cao Q, et al. Insulin growth factor-1 (IGF-1) enhances hippocampal excitatory and seizure activity through IGF-1 receptor-mediated mechanisms in the epileptic brain. Clinical Science, 2015, 129(12): 1047-1060.
10. Glazova MV, Nikitina LS, Hudik KA, et al. Inhibition of ERK1/2 signaling prevents epileptiform behavior in rats prone to audiogenic seizures. Journal of Neurochemistry, 2015, 132(2): 218-229.
11. Zu-Cai Xu, Yang-Mei Chen, Ping Xu, et al. Epileptiform Discharge Upregulates P-Erk1/2, Growth-Associated Protein 43 and Synaptophysin in Cultured Rat Hippocampal Neurons. Seizure, 2009, 18 (9): 680-685.
12. Orlova KA, Crino PB. The tuberous sclerosis complex. Annals of the New York Academy of Sciences, 2010, 1184(1): 87-105.
13. Goto J, Talos DM, Klein P, et al. Regulable neural progenitor-specific Tsc1 loss yields giant cells with organellar dysfunction in a model of tuberous sclerosis complex. Proceedings of the National Academy of Sciences, 2011, 108(45): E1070-E1079.
14. Zhang L, Bartley CM, Gong X, et al. MEK-ERK1/2-dependent FLNA overexpression promotes abnormal dendritic patterning in tuberous sclerosis independent of mTOR. Neuron, 2014, 84(1): 78-91.
15. Alhaj MW, Zaitone SA, Moustafa YM. Fluvoxamine alleviates seizure activity and downregulates hippocampal GAP-43 expression in pentylenetetrazole-kindled mice: role of 5-HT3 receptors. Behavioural Pharmacology, 2015, 26(4): 369-382.
16. Latchney SE, Masiulis I, Zaccaria KJ, et al. Developmental and adult GAP-43 deficiency in mice dynamically alters hippocampal neurogenesis and mossy fiber volume. Developmental Neuroscience, 2014, 36(1): 44-63.
17. Decker JM, Krüger L, Sydow A, et al. Pro-aggregant Tau impairs mossy fiber plasticity due to structural changes and Ca dysregulation. Acta Neuropathologica Communications, 2015, 1(3): 1-18.
18. Kandratavicius L, Monteiro MR, Assirati Jr JA, et al. Neurotrophins in mesial temporal lobe epilepsy with and without psychiatric comorbidities. Journal of Neuropathology & Experimental Neurology, 2013, 72(11): 1029-1042.
19. Xu ZC, Chen YM, Xu P, et al. Epileptiform discharge upregulates p-ERK1/2, growth-associated protein 43 and synaptophysin in cultured rat hippocampal neurons. Seizure, 2009, 18(10): 680-685.
20. Hu B, Liu C, Bramlett H, et al. Changes in trkB-ERK1/2-CREB/Elk-1 pathways in hippocampal mossy fiber organization after traumatic brain injury. Journal of Cerebral Blood Flow & Metabolism, 2004, 24(8): 934.
21. Shomit Sengupta, Timothy R Peterson, David M Sabatini. Regulation of the mtor complex 1 pathway by nutrients, growth factors, and stress. Molecular Cell, 2010, 40 (21): 310-322.
22. Catherine A Vickers, Kirsten S Dickson, David JA Wyllie. Induction and maintenance of late-phase long-term potentiation in isolated dendrites of rat hippocampal ca1 pyramidal neurones. The Journal of Physiology, 2005, 568 (17): 803-813.
23. Yunfei Huang, Bingnan N Kang, Jing Tian, et al. The Cationic Amino Acid Transporters Cat1 and Cat3 Mediate Nmda Receptor Activation-Dependent Changes in Elaboration of Neuronal Proces Via the Mammalian Target of Rapamycin Mtor Pathway. The Journal of Neuroscience, 2007, 27 (10): 449-458.
24. Russo E, Citraro R, Donato G, et al. mTOR inhibition modulates epileptogenesis, seizures and depressive behavior in a genetic rat model of absence epilepsy. Neuropharmacology, 2013, 69(12): 25-36.
25. Wong M. Mammalian target of rapamycin (mTOR) inhibition as a potential antiepileptogenic therapy: from tuberous sclerosis to common acquired epilepsies. Epilepsia, 2010, 51(1): 27-36.
26. Wang SJ, Bo QY, Zhao XH, et al. Resveratrol pre-treatment reduces early inflammatory responses induced by status epilepticus via mTOR signaling. Brain Research, 2013, 1492(1): 122-129.
27. Tang H, Long H, Zeng C, et al. Rapamycin suppresses the recurrent excitatory circuits of dentate gyrus in a mouse model of temporal lobe epilepsy. Biochemical and Biophysical Research Communications, 2012, 420(1): 199-204.
28. Zhou J, Blundell J, Ogawa S, et al. Pharmacological inhibition of mTORC1 suppresses anatomical, cellular, and behavioral abnormalities in neural-specific Pten knock-out mice. The Journal of Neuroscience, 2009, 29(6): 1773-1783.
29. Meikle L, Pollizzi K, Egnor A, et al. Response of a neuronal model of tuberous sclerosis to mammalian target of rapamycin (mTOR) inhibitors: effects on mTORC1 and Akt signaling lead to improved survival and function. The Journal of Neuroscience, 2008, 28(21): 5422-5432.
30. Buckmaster PS, Ingram EA, Wen X. Inhibition of the mammalian target of rapamycin signaling pathway suppresses dentate granule cell axon sprouting in a rodent model of temporal lobe epilepsy. The Journal of Neuroscience, 2009, 29(25): 8259-8269.
31. Ling-Hui Zeng, Nicholas R Rensing, Michael Wong. The Mammalian Target of Rapamycin Signaling Pathway Mediates Epileptogenesis in a Model of Temporal Lobe Epilepsy. The Journal of Neuroscience, 2009, 29 (20): 6964-6972.
32. Felicia H Lew, Paul S Buckmaster. Is There a Critical Period for Mossy Fiber Sprouting in a Mouse Model of Temporal Lobe Epilepsy?. Epilepsia, 2011, 52 (11): 2326-2332.
33. Haiyun Tang, Hongyu Long, Chang Zeng, et al. Rapamycin Suppresses the Recurrent Excitatory Circuits of Dentate Gyrus in a Mouse Model of Temporal Lobe Epilepsy. Biochemical and Biophysical Research Communications, 2012, 420 (32): 199-204.
34. Jonas Dyhrfjeld-Johnsen, Vijayalakshmi Santhakumar, Robert J Morgan, et al. Topological Determinants of Epileptogenesis in Large-Scale Structural and Functional Models of the Dentate Gyrus Derived from Experimental Data. Journal of Neurophysiology, 2007, 97 (11): 1566-1587.
35. Kron MM, Zhang H, Parent JM. The developmental stage of dentate granule cells dictates their contribution to seizure-induced plasticity. The Journal of Neuroscience, 2010, 30(6): 2051-2059.
36. Lew FH, Buckmaster PS. Is there a critical period for mossy fiber sprouting in a mouse model of temporal lobe epilepsy? Epilepsia, 2011, 52(12): 2326-2332.
37. Heng K, Haney MM, Buckmaster PS. High‐dose rapamycin blocks mossy fiber sprouting but not seizures in a mouse model of temporal lobe epilepsy. Epilepsia, 2013, 54(9): 1535-1541.
38. Huang X, Zhang H, Yang J, et al. Pharmacological inhibition of the mammalian target of rapamycin pathway suppresses acquired epilepsy. Neurobiology of Disease, 2010, 40(1): 193-199.
39. Zeng L-H, Rensing NR, Wong M. The mammalian target of rapamycin signaling pathway mediates epileptogenesis in a model of temporal lobe epilepsy. The Journal of Neuroscience, 2009, 29(21): 6964-6972.
40. Sliwa A, Plucinska G, Bednarczyk J, et al. Post-treatment with rapamycin does not prevent epileptogenesis in the amygdala stimulation model of temporal lobe epilepsy. Neuroscience Letters, 2012, 509(2): 105-109.

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