Drosophila seizure disorders: genetic suppression of seizure susceptibility

doi:10.1007/s11515-016-1395-1

Front. Biol.

2016, Vol. 11

Issue (2) : 96-108 https://doi.org/10.1007/s11515-016-1395-1

REVIEW

Drosophila seizure disorders: genetic suppression of seizure susceptibility

Arunesh Saras¹,Laura E. Simon¹,Harlan J. Brawer¹,Richard E. Price²,Mark A. Tanouye^1,^2,^3,^*(

)

1. Division of Organismal Biology, Department of Environmental Science, Policy and Management, University of California, Berkeley, CA 94720, USA
2. Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA
3. Helen Wills Neuroscience Institute, University of California, Berkeley, CA 94720, USA

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Abstract

Various Drosophila models of human disease have recently received increased interest. The main goal is to uncover the fundamental biological basis for human pathology taking advantage of the power of Drosophila genetics. This review examines a set of Drosophila seizure-sensitive mutations that model human seizure disorders, especially epilepsy. Also described is a novel set of mutations that act as seizure-suppressors that ameliorate epilepsy phenotypes in double mutant combinations.

Keywords Drosophila epilepsy seizure disorders sodium channel seizure-suppressor genes

Corresponding Author(s): Mark A. Tanouye

Just Accepted Date: 06 April 2016 Online First Date: 25 April 2016 Issue Date: 17 May 2016

Cite this article:

Arunesh Saras,Laura E. Simon,Harlan J. Brawer, et al. Drosophila seizure disorders: genetic suppression of seizure susceptibility[J]. Front. Biol., 2016, 11(2): 96-108.

URL:

https://academic.hep.com.cn/fib/EN/10.1007/s11515-016-1395-1
https://academic.hep.com.cn/fib/EN/Y2016/V11/I2/96

Fig.1 legend. Drosophila cac^TS2 electrophysiology. (A) Electrical recording from a cac^TS2 DLM fiber showing that seizure-like activity is not evoked by stimulation at 30V HFS, near the wild-type range. (B) Seizure-like activity is observed in cac^TS2 at a larger stimulus voltage of 50V HFS, indicating that the mutant is seizure-resistant. (C) Spontaneous seizure-like activity observed in cac^TS2 when the temperature is increased to 38°, indicating that the mutant is seizure-sensitive at restrictive temperatures. Recording shows a representative example of three spontaneous seizure-like discharges. Enlargement (lower trace) shows one of the spontaneous discharges at a higher sweep speed. (D) Recording from a sda DLM fiber showing seizure-like activity evoked by a 10V HFS stimulus. (E) Recording from a cac^TS2; sda DLM fiber showing that a 15V HFS stimulation does not evoke seizure-like activity at this voltage; the double mutant shows a higher threshold indicating seizure-suppression by cac^TS2. (F) Recording from a cac^TS2; sda DLM fiber showing that seizure-like activity is evoked at 20V HFS. Horizontal calibration: 300 msec for C (upper trace); 150 msec. for A-B, C (inset), D-F; Vertical calibration: 20mV.

Tab.1 Drosophila seizure-sensitive mutants and their gene products

Tab.2 Human epilepsy genes causing seizure phenotypes in homologous or similar fly genes

Tab.3 Seizure-suppressor mutants and their gene products

Fig.2 A model for seizure suppression in Drosophila. This model consists of three presynaptic input circuits that act to trigger seizures (labeled Wt, Bs, and Su). These inputs drive a “trigger circuit” that is capable of delivering seizures throughout the Drosophila central nervous system via an “output circuit.” It is the threshold of the trigger circuit that determines the seizure threshold for each individual fly. Although the input circuits are given separate names, we have found no qualitative features that distinguish them. In a normal wild type fly, stimulation of two input (say, Bs and Wt) with an HFS electrical stimulus wavetrain triggers a seizure. Synaptic potentials from Bs and Wt summate temporally and spatially in the trigger circuit to generate the seizure. In a BS mutant fly, it is much easier to trigger a seizure and stimulation of only the Bs input is sufficient to bring the trigger circuit to threshold. Many suppressor mutants are also seizure resistant; it is more difficult to trigger the seizure, and necessary to drive all three inputs (Bs, Wt, and Su). In many BS; suppressor double mutant genotypes, seizure threshold has been restored to near the wild type level and a seizure is triggered by stimulating two inputs (say, Bs and Wt). We are presuming that larger stimulation voltages drive greater numbers of input neurons since single cell excitability appears to remain unchanged across different wild type and mutant strains (Kuebler et al., 2001).

1a	Barreto E, Cressman J R (2011). Ion concentration dynamics as a mechanism for neuronal bursting. J Biol Phys, 37(3): 361–373
1	Bassuk A G, Wallace R H, Buhr A, Buller A R, Afawi Z, Shimojo M, Miyata S, Chen S, Gonzalez-Alegre P, Griesbach H L, Wu S, Nashelsky M, Vladar E K, Antic D, Ferguson P J, Cirak S, Voit T, Scott M P, Axelrod J D, Gurnett C, Daoud A S, Kivity S, Neufeld M Y, Mazarib A, Straussberg R, Walid S, Korczyn A D, Slusarski D C, Berkovic S F, El-Shanti H I (2008). A homozygous mutation in human PRICKLE1 causes an autosomal-recessive progressive myoclonus epilepsy-ataxia syndrome. Am J Hum Genet, 83(5): 572–581 https://doi.org/10.1016/j.ajhg.2008.10.003
2	Ben-Ari Y (2002). Excitatory actions of GABA during development: the nature of the nurture. Nature, 3: 728–739
3	Ben-Ari Y, Gaiarsa J L, Tyzio R, Khazipov R (2007). GABA: a pioneer transmitter that excites immature neurons and generates primitive oscillations. Physiol Rev, 87(4): 1215–1284 https://doi.org/10.1152/physrev.00017.2006
4	Benzer S (1971). From the gene to behavior. JAMA, 218(7): 1015–1022 https://doi.org/10.1001/jama.1971.03190200047010
5	Boettger T, Rust M B, Maier H, Seidenbecher T, Schweizer M, Keating D J, Faulhaber J, Ehmke H, Pfeffer C, Scheel O, (2003). Loss of K-Cl co-transporter KCC3 causes deafness, neurodegeneration and reduced seizure threshold. EMBO J, 22(20): 5422–5434 https://doi.org/10.1093/emboj/cdg519
6	Bullock T H, Horridge G A (1965). “Structure and Function in the Nervous System of Invertebrates”, 2 vol. San Francisco and London: W H Freeman A Comp Ltd, XXVIII, 1722pp
7	Carlson S D, Juang J L, Hilgers S L, Garment M B (2000). Blood barriers of the insect. Annu Rev Entomol, 45(1): 151–174 https://doi.org/10.1146/annurev.ento.45.1.151
8	Catterall W A (2014). Sodium channels, inherited epilepsy, and antiepileptic drugs. Annu Rev Pharmacol Toxicol, 54(1): 317–338 https://doi.org/10.1146/annurev-pharmtox-011112-140232
9	Catterall W A, Goldin A L, Waxman S G (2003). International Union of Pharmacology, XXXIX Compendium of voltage-gated ion channels: sodium channels. Pharmacol Rev, 55(4): 575–578 https://doi.org/10.1124/pr.55.4.7
10	Champoux J J (2001). DNA topoisomerases: Structure, function and mechanism. Annu Rev Biochem, 70(1): 369–413 https://doi.org/10.1146/annurev.biochem.70.1.369
11	Chung H, Sztal T, Pasricha S, Sridhar M, Batterham P, Daborn P J (2009). Characterization of Drosophila melanogaster cytochrome P450 genes. Proc Natl Acad Sci USA, 106(14): 5731–5736 https://doi.org/10.1073/pnas.0812141106
12	Chvatal A, Sykova E (2000). Glial influence on neuronal signaling. Prog Brain Res, 125: 199–216 https://doi.org/10.1016/S0079-6123(00)25011-5
13	Cressman J RJr, Ullah G, Ziburkus J, Schiff S J, Barreto E (2009). The influence of sodium and potassium dynamics on excitability, seizures, and the stability of persistent states: I. single neuron dynamics. J Comput Neurosci, 26(2): 159–170 https://doi.org/10.1007/s10827-008-0132-4
14	D'Ambrosio R (2004). The role of glial membrane ion channels in seizures and epileptogenesis. Pharmacol Ther, 103(2): 95–108 https://doi.org/10.1016/j.pharmthera.2004.05.004
15	Devinsky O, Vezzani A, Najjar S, De Lanerolle N C, Rogawski M A (2013). Glia and epilepsy: excitability and inflammation. Trends Neurosci, 36(3): 174–184 https://doi.org/10.1016/j.tins.2012.11.008
16	DiMauro S, Hirano M, Kaufmann P, Tanji K, Sano M, Shungu D C, Bonilla E, DeVivo D C, (2002). Clinical features and genetics of myoclonic epilepsy with ragged red fibers. Adv Neurol, 89: 217–229
17	Dong K (2007). Insect sodium channels and insecticide resistance. Invert Neurosci, 7(1): 17–30 https://doi.org/10.1007/s10158-006-0036-9
18	Engel J E, Wu C F (1994). Altered mechanoreceptor response in Drosophila bang-sensitive mutants. J Comp Physiol A Neuroethol Sens Neural Behav Physiol, 175(3): 267–278 https://doi.org/10.1007/BF00192986
19	Fahmy O G, Fahmy M J (1960). Cytogenetic analysis of the action of carcinogens and tumor inhibitors in Drosophila melanogaster. Genetics, 45: 419–438
20	Feng G, Deak P, Chopra M, Hall L M (1995). Cloning and functional analysis of TipE, a novel membrane protein that enhances Drosophila para sodium channel function. Cell, 82(6): 1001–1011 https://doi.org/10.1016/0092-8674(95)90279-1
21	Fergestad T, Bostwick B, Ganetzky B (2006). Metabolic disruption in Drosophila bang-sensitive seizure mutants. Genetics, 173(3): 1357–1364 https://doi.org/10.1534/genetics.106.057463
22	Fertziger A P, Ranck J BJr (1970). Potassium accumulation in interstitial space during epileptiform seizures. Exp Neurol, 26(3): 571–585 https://doi.org/10.1016/0014-4886(70)90150-0
23	Florence G, Dahlem M A, Almeida A C G, Bassani J W M, Kurths J (2009). The role of extracellular potassium dynamics in the different stages of ictal bursting and spreading depression: a computational study. J Theor Biol, 258(2): 219–228 https://doi.org/10.1016/j.jtbi.2009.01.032
24	Freeman A A, Syed S, Sanyal S (2013). Modeling the genetic basis for human sleep disorders in Drosophila. Commun Integr Biol, 6(1): e22733 https://doi.org/10.4161/cib.22733
25	Ganetzky B (1984). Genetic studies of membrane excitability in Drosophila: lethal interaction between two temperature-sensitive paralytic mutations. Genetics, 108: 897–911
26	Ganetzky B, Wu C F (1982a). Indirect suppression involving behavioral mutants with altered nerve excitability in Drosophila melanogaster. Genetics, 100: 597–614
27	Ganetzky B, Wu C F (1982b). Drosophila mutants with opposing effects on nerve excitability: genetic and spatial interactions in repetitive firing. J Neurophysiol, 47: 501–514
28	Glasscock E, Singhania A, Tanouye M A (2005). The mei-p26 gene encodes an RBCC-NHL protein that regulates seizure susceptibility in Drosophila. Genetics, 170: 1677–1689 https://doi.org/10.1534/genetics.105.043174
29	Glasscock E, Tanouye M A (2005). Drosophila couch potato mutants exhibit complex neurological abnormalities including epilepsy phenotypes. Genetics, 169(4): 2137–2149 https://doi.org/10.1534/genetics.104.028357
30	Goldin A L (2001). Resurgence of sodium channel research. Annu Rev Physiol, 63(1): 871–894 https://doi.org/10.1146/annurev.physiol.63.1.871
31	Greenhill S D, Jones R S G (2010). Diverse antiepileptic drugs increase the ratio of background synaptic inhibition to excitation and decrease neuronal excitability in neurons of the rat entorhinal cortex in vitro. Neurosci, 167(2): 456–474 https://doi.org/10.1016/j.neuroscience.2010.02.021
32	Griesemer D A, Kellner C H, Beale M D, Smith G M (1997). Electroconvulsive therapy for treatment of intractable seizures: initial findings in two children. Neurology, 49(5): 1389–1392 https://doi.org/10.1212/WNL.49.5.1389
33	Grigliatti T A, Hall L, Rosenbluth R, Suzuki D T (1973). Temperature-sensitive mutations in Drosophila melanogaster. Mol Gen Genet, 120(2): 107–114 https://doi.org/10.1007/BF00267238
34	Guo M (2012). Drosophila as a model to study mitochondrial dysfunction in Parkinson’s disease. Cold Spring Harb Perspect Med, 2(11): a009944 https://doi.org/10.1101/cshperspect.a009944
35	Hariharan I K, Haber D A (2003). Yeast, flies, worms, and fish in the study of human disease. N Engl J Med, 348(24): 2457–2463 https://doi.org/10.1056/NEJMon023158
36	Hebert S C, Mount D B, Gamba G (2004). Molecular physiology of cation-coupled Cl– cotransport: the SLC12 family. Pflugers Arch, 447(5): 580–593 https://doi.org/10.1007/s00424-003-1066-3
37	Hekmat-Scafe D S, Lundy M Y, Ranga R, Tanouye M A (2006). Mutations in the K+/Cl– cotransporter gene kazachoc (kcc) increase seizure susceptibility in Drosophila. J Neurosci, 26(35): 8943–8954 https://doi.org/10.1523/JNEUROSCI.4998-05.2006
38	Hekmat-Scafe D S, Mercado A, Fajilan A A, Lee A W, Hsu R, Mount D B, Tanouye M A (2010). Seizure sensitivity is ameliorated by targeted expression of K+-Cl– cotransporter function in the mushroom body of the Drosophila brain. Genetics, 184(1): 171–183 https://doi.org/10.1534/genetics.109.109074
39	Hirth F (2010). Drosophila melanogaster in the study of human neurodegeneration. CNS Neurol Disord Drug Targets, 9(4): 504–523 https://doi.org/10.2174/187152710791556104
40	Howlett I C, Tanouye M A (2013). Seizure-sensitivity in Drosophila is ameliorated by dorsal vessel injection of the antiepileptic drug valproate. J Neurogenet, 27(4): 143–150 https://doi.org/10.3109/01677063.2013.817574
41	Hubner C A, Stein V, Hermans-Borgmeyer I, Meyer T, Ballanyi K, Jentsch T J (2001). Disruption of KCC2 reveals an essential role of K-Cl cotransport already in early synaptic inhibition. Neuron, 30(2): 515–524 https://doi.org/10.1016/S0896-6273(01)00297-5
42	Imbrici P, Jaffe S L, Eunson L H, Davies N P, Herd C, Robertson R, Kullmann D M, Hanna M G (2004). Dysfunction of the brain calcium channel CaV2.1 in absence epilepsy and episodic ataxia. Brain, 127(12): 2682–2692 https://doi.org/10.1093/brain/awh301
43	Jacobs J, Dubeau F, Olivier A, Andermann F (2008). Pathways of seizure propagation from the temporal to the occipital lobe. Epileptic Disord, 10: 266–270
44a	Kager H, Wadman W J, Somjen G G (2000). Simulated seizures and spreading depression in a neuron model incorporating interstitial space and ion concentrations. J Neurophysiol, 84(1): 195–512
44	Kandel E R, Spencer W A (1961). The pyramidal cell during hippocampal seizure. Epilepsia, 2(1): 63–69 https://doi.org/10.1111/j.1528-1167.1961.tb06247.x
45	Kawasaki F, Felling R, Ordway R W (2000). A temperature-sensitive paralytic mutant defines a primary synaptic calcium channel in Drosophila. J Neurosci, 20: 4885–4889
46	Kitamoto T (2001). Conditional modification of behavior in Drosophila by targeted expression of a temperature-sensitive shibire allele in defined neurons. J Neurobiol, 47(2): 81–92 https://doi.org/10.1002/neu.1018
47	Koenig J H, Ikeda K (1989). Disappearance and reformation of synaptic vesicle membrane upon transmitter release observed under reversible blockage of membrane retrieval. J Neurosci, 9: 3844–3860
48	Kroll J R, Wong K G, Siddiqui F M, Tanouye M A (2015). Disruption of endocytosis with the dynamin mutant shibirets1 suppresses seizures in Drosophila. Genetics, 201(3): 1087–1102 https://doi.org/10.1534/genetics.115.177600
49	Kuebler D, Tanouye M A (2000). Modifications of seizure susceptibility in Drosophila. J Neurophysiol, 83: 998–1009
50	Kuebler D, Tanouye M A (2002). The anticonvulsant sodium valproate reduces seizure-susceptibility in mutant Drosophila. Brain Res, 958(1): 36–42 https://doi.org/10.1016/S0006-8993(02)03431-5
51	Kuebler D, Zhang H, Ren X, Tanouye M A (2001). Genetic suppression of seizure susceptibility in Drosophila. J Neurophysiol, 86: 1211–1225
52	Kuromi H, Honda A, Kidokoro Y (2004). Ca2<?A3B2 h=-0.3h?>+ influx through distinct routes controls exocytosis and endocytosis at Drosophila presynaptic terminals. Neuron, 41(1): 101–111 https://doi.org/10.1016/S0896-6273(03)00815-8
53	Kwan P, Brodie M J (2000). Early identification of refractory epilepsy. N Engl J Med, 342(5): 314–319 https://doi.org/10.1056/NEJM200002033420503
54	Landmark C J (2008). Targets for antiepileptic drugs in the synapse. Med Sci Monit, 13: RA1–RA7
55	Lee J, Wu C F (2002). Electroconvulsive seizure behavior in Drosophila: analysis of the physiological repertoire underlying a stereotyped action pattern in bang sensitive mutants. J Neurosci, 22: 11065–11079
56	Lee J, Wu C F (2006). Genetic modifications of seizure susceptibility and expression by altered excitability in Drosophila Na(+) and K(+) channel mutants. J Neurophysiol, 96(5): 2465–2478 https://doi.org/10.1152/jn.00499.2006
57	Lilly M, Carlson J (1990). smellblind: a gene required for Drosophila olfaction. Genetics, 124: 293–302
58	Lin W H, Baines R A (2014). Regulation of membrane excitability: a convergence on voltage-gated sodium conductance. Molec Neurobiol, 10.1007/s12035-014-8674-0 /fulltext.html
59	Lin W H, Wright D E, Muraro N I, Baines R A (2009). Alternative splicing in the voltage-gated sodium channel DmNav regulates activation, inactivation, and persistent current. J Neurophysiol, 102(3): 1994–2006 https://doi.org/10.1152/jn.00613.2009
60	Loscher W (2002). Basic pharmacology of valproate: a review after 35 years of clinical use for the treatment of epilepsy. CNS Drugs, 16: 669–694 https://doi.org/10.2165/00023210-200216100-00003
61	Lossin C (2009). A catalog of SCN1A variants. Brain Dev, 31(2): 114–130 https://doi.org/10.1016/j.braindev.2008.07.011
62	Loughney K, Kreber R, Ganetzky B (1989). Molecular analysis of the para locus, a sodium channel gene in Drosophila. Cell, 58(6): 1143–1154 https://doi.org/10.1016/0092-8674(89)90512-6
63	Lunde M E, Lee E K, Rasmussen K G (2006). Electroconvulsive therapy in patients with epilepsy. Epilepsy Behav, 9(2): 355–359 https://doi.org/10.1016/j.yebeh.2006.06.013
64	Mayer F, Mayer N, Chinn L, Pinsonneault R L, Kroetz D, Bainton R J (2009). Evolutionary conservation of vertebrate blood-brain barrier chemoprotective mechanisms in Drosophila. J Neurosci, 29(11): 3538–3550 https://doi.org/10.1523/JNEUROSCI.5564-08.2009
65	McIntyre D C, Gilby K L (2008). Mapping seizure pathways in the temporal lobe. Epilepsia, 49(s3Suppl 3): 23–30 https://doi.org/10.1111/j.1528-1167.2008.01507.x
66	McNamara J O (1994). Cellular and molecular basis of epilepsy. J Neurosci, 14: 3413–3425
67	Mount D B, Delpire E, Gamba G, Hall A E, Poch E, Hoover R S, Herbert S C (1998). The electroneutral cation-chloride cotransporters. J Exp Biol, 201: 2091–2102
68	Mulley J C, Scheffer I E, Petrou S, Dibbens L M, Berkovic S F, Harkin L A (2005). SCN1A mutations and epilepsy. Hum Mutat, 25(6): 535–542 https://doi.org/10.1002/humu.20178
69	Noebels J L (1996). Targeting epilepsy genes. Neuron, 16(2): 241–244 https://doi.org/10.1016/S0896-6273(00)80042-2
70	O’Dowd D K, Gee J R, Smith M A (1995). Sodium current density correlates with expression of specific alternatively spliced sodium channel mRNAs in single neurons. J Neurosci, 15: 4005–4012
71	Oh C Y, Bainbridge J (2012). Lowering the seizure threshold associated with antidepressants, stimulants, antipsychotics, and others. Mental Health Clinician: November 2012-Epilepsy and seizure disorders and their treatment, Vol. 2, No. 5, pp. 127–128
72	Olson R O, Liu Z, Nomura Y, Song W, Dong K (2008). Molecular and functional characterization of voltage-gated sodium channel variants from Drosophila melanogaster. Insect Biochem Mol Biol, 38(5): 604–610 https://doi.org/10.1016/j.ibmb.2008.01.003
73	Paemka L, Mahajan V B, Ehaideb S N, Skeie J M, Tan M C, Wu S, Cox A J, Sowers L P, Gecz J, Jolly L, Ferguson P J, Darbro B, Schneider A, Scheffer I E, Carvill G L, Mefford H C, El-Shanti H, Wood S A, Manak J R, Bassuk A G (2015). Seizures are regulated by ubiquitin-specific peptidase 9 X-linked (USP9X), a de-ubiquitinase. PLoS Genet, 11(3): e1005022 https://doi.org/10.1371/journal.pgen.1005022
74	Parker L, Padilla M, Du Y, Dong K, Tanouye M A (2011). Drosophila as a model for epilepsy: bss is a gain-of-function mutation in the Para sodium channel gene that leads to seizures. Genetics, 187(2): 523–534 https://doi.org/10.1534/genetics.110.123299
75	Pavlidis P, Ramaswami M, Tanouye M A (1994). The Drosophila easily shocked gene: a mutation in a phospholipid synthetic pathway causes seizure, neuronal failure, and paralysis. Cell, 79(1): 23–33 https://doi.org/10.1016/0092-8674(94)90397-2
76	Pavlidis P, Tanouye M A (1995). Seizures and failures in the giant fiber pathway of Drosophila bang-sensitive paralytic mutants. J Neurosci, 15: 5810–5819
77	Pfeiffer B D, Truman J W, Rubin G M (2012). Using translational enhancers to increase transgene expression in Drosophila. Proc Natl Acad Sci USA, 109(17): 6626–6631 https://doi.org/10.1073/pnas.1204520109
78	Phelan P, Nakagawa M, Wilkin M B, Moffat K G, O’Kane C J, Davies J A, Bacon J P (1996). Mutations in shaking-B prevent electrical synapse formation in the Drosophila giant fiber system. J Neurosci, 16: 1101–1113
79	Phelan P, Starich T A (2001). Innexins get into the gap. BioEssays, 23(5): 388–396 https://doi.org/10.1002/bies.1057
80	Phelan P, Stebbings L A, Baines R A, Bacon J P, Davies J A, Ford C (1998). Drosophila shaking-B protein forms gap junctions in paired Xenopus oocytes. Nature, 391(6663): 181–184 https://doi.org/10.1038/34426
81	Pisani F, Oteri G, Costa C, Di Raimando G, Di Perri R (2002). Effects of psychotropic drugs on seizure threshold. Drug Saf, 25(2): 91–110 https://doi.org/10.2165/00002018-200225020-00004
82	Pittendrigh B, Reenan R, ffrench-Constant R H, Ganetzky B (1997). Point mutations in the Drosophila sodium channel gene para associated with resistance to DDT and pyrethroid insecticides. Mol Gen Genet, 356(6): 602–610 https://doi.org/10.1007/s004380050608
83	Ramaswami M, Tanouye M A (1989). Two sodium channel genes in Drosophila: implications for channel diversity. Proc Natl Acad Sci USA, 86(6): 2079–2082 https://doi.org/10.1073/pnas.86.6.2079
84	Read R (2011). Drosophila melanogaster as a model system for human brain cancers. Glia, 59(9): 1364–1376 https://doi.org/10.1002/glia.21148
85	Regenold W T, Weintraub D, Taller A (1998). Electroconvulsive therapy for epilepsy and major depression. Am J Geriatr Psychiatry, 6(2): 180–183(Top of Form) https://doi.org/10.1097/00019442-199805000-00012
86	Rein K, Zöckler M, Mader M T, Grübel C, Heisenberg M (2002). The Drosophila standard brain. Curr Biol, 12(3): 227–231 https://doi.org/10.1016/S0960-9822(02)00656-5
87	Reiter L T, Bier E (2001). Using Drosophila melanogaster to uncover human disease gene function and potential drug target proteins. Expert Opin Ther Targets, 6: 387–399
88	Reynolds E R, Stauffer E A, Feeney L, Rojahn E, Jacobs B, McKeever C (2003). Treatment with the antiepileptic drugs phenytoin and gabapentin ameliorates seizure and paralysis of Drosophila bang-sensitive mutants. J Neurobiol, 58(4): 503–513 https://doi.org/10.1002/neu.10297
89	Rieckhof G E, Yoshihara M, Guan Z, Littleton J T (2003). Presynaptic N-type calcium channels regulate synaptic growth. J Biol Chem, 278(42): 41099–41108 https://doi.org/10.1074/jbc.M306417200
90	Royden C S, Pirrotta V, Jan L Y (1987). The tko locus, site of a behavioral mutation in D. melanogaster, codes for a protein homologous to prokaryotic ribosomal protein S12. Cell, 51(2): 165–173 https://doi.org/10.1016/0092-8674(87)90144-9
91	Rusan Z M, Kingsford O A, Tanouye M A (2014). Modeling glial contributions to seizures and epileptogenesis: cation-chloride cotransporters in Drosophila melanogaster. PLoS ONE, 9(6): e101117 https://doi.org/10.1371/journal.pone.0101117
92	Sackeim H A, Decina P, Prohovnik I, Malitz S S R, Resor S R (1987). Anticonvulsant and antidepressant properties of electroconvulsive therapy: a proposed mechanism of action. Biol Psychiatry, 18: 1301–1310
93	Salkoff L, Kelly L (1978). Temperature-induced seizure and frequency-dependent neuromuscular block in a ts mutant of Drosophila. Nature, 273(5658): 156–158 https://doi.org/10.1038/273156a0
94	Saras A, Tanouye M A (2016). Mutations of the calcium channel gene cacophony suppress seizures in Drosophila. PLoS Genet, 12(1): e1005784 https://doi.org/10.1371/journal.pgen.1005784
95	Schutte R J, Schutte S S, Algara J, Barragan E V, Gilligan J, Staber C, Savva Y A, Smith M A, Reenan R, O’Dowd D K (2014). Knock-in model of Dravet syndrome reveals a constitutive and conditional reduction in sodium current. J Neurophysiol, 112(4): 903–912 https://doi.org/10.1152/jn.00135.2014
96	Schwarz N, Hahn A, Bast T, Müller S, Löffler H, Maljevic S, Gaily E, Prehl I, Biskup S, Joensuu T, Lehesjoki A E, Neubauer B A, Lerche H, Hedrich U B (2016). Mutations in the sodium channel gene SCN2A cause neonatal epilepsy with late-onset episodic ataxia. J Neurol, 263(2): 334–343 https://doi.org/10.1007/s00415-015-7984-0
97	Sehgal A, Mignot E (2011). Genetics of sleep and sleep disorders. Cell, 146(2): 194–207 https://doi.org/10.1016/j.cell.2011.07.004
98	Seifert G, Carmignoto G, Steinhäuser C (2010). Astrocyte dysfunction in epilepsy. Brain Res Brain Res Rev, 63(1-2): 212–221 https://doi.org/10.1016/j.brainresrev.2009.10.004
99	Shneker B F, Fountain N B (2003). Epilepsy. Dis Mon, 49(7): 426–478 https://doi.org/10.1016/S0011-5029(03)00065-8
100	Siddiqi O, Benzer S (1976). Neurophysiological defects in temperature-sensitive paralytic mutants of Drosophila melanogaster. Proc Natl Acad Sci USA, 73(9): 3253–3257 https://doi.org/10.1073/pnas.73.9.3253
101	Smith L A, Wang X, Peixoto A A, Neumann E K, Hall L M, Hall J C (1996). A Drosophila calcium channel alpha1 subunit gene maps to a genetic locus associated with behavioral and visual defects. J Neurosci, 16: 7868–7879
102	Somjen G G (2004). “Ions in the Brain : Normal Function, Seizures, and Stroke: Normal Function, Seizures, and Stroke”. Oxford University Press, USA. At<>
103	Song J, Hu J, Tanouye M A (2007). Seizure suppression by top1 mutations in Drosophila. J Neurosci, 27(11): 2927–2937 https://doi.org/10.1523/JNEUROSCI.3944-06.2007
104	Song J, Parker L, Hormozi L, Tanouye M A (2008). DNA topoisomerase I inhibitors ameliorate seizure-like behaviors and paralysis in a Drosophila model of epilepsy. Neuroscience, 156(3): 722–728 https://doi.org/10.1016/j.neuroscience.2008.07.024
105	Song J, Tanouye M A (2006). Seizure suppression by shakB2, a gap junction mutation in Drosophila. J Neurophysiol, 95(2): 627–635 https://doi.org/10.1152/jn.01059.2004
106	Song J, Tanouye M A (2007). Role for para sodium channel gene 3′ UTR in the modification of Drosophila seizure susceptibility. Dev Neurobiol, 67(14): 1944–1956 https://doi.org/10.1002/dneu.20519
107	Stefan H, Lopes da Silva F H (2013). Epileptic neuronal networks: methods of identification and clinical relevance. Front Neurol, 4: 8 https://doi.org/10.3389/fneur.2013.00008
108	Steinhoff B, Hirsch E, Mutani R, Nakken K (2003). The ideal characteristics of antiepileptic therapy: an overview of old and new AEDs. Acta Neurol Scand, 107(2): 87–95 https://doi.org/10.1034/j.1600-0404.2003.01311.x
109	Stilwell G E, Saraswati S, Littleton J T, Chouinard S W (2006). Development of a Drosophila seizure model for in vivo high-throughput drug screening. Eur J Neurosci, 24(8): 2211–2222 https://doi.org/10.1111/j.1460-9568.2006.05075.x
110	Stödberg T, McTague A, Ruiz A J, Hirata H, Zhen J, Long P, Farabella I, Meyer E, Kawahara A, Vassallo G, Stivaros S M, Bjursell M K, Stranneheim H, Tigerschiöld S, Persson B, Bangash I, Das K, Hughes D, Lesko N, Lundeberg J, Scott R C, Poduri A, Scheffer I E, Smith H, Gissen P, Schorge S, Reith M E, Topf M, Kullmann D M, Harvey R J, Wedell A, Kurian M A (2015). Mutations in SLC12A5 in epilepsy of infancy with migrating focal seizures. Nat Commun, 6: 8038 https://doi.org/10.1038/ncomms9038
111	Stork T, Engelen D, Krudewig A, Silies M, Bainton R J, Klambt C (2008). Organization and function of the blood-brain barrier in Drosophila. J Neurosci, 28(3): 587–597 https://doi.org/10.1523/JNEUROSCI.4367-07.2008
112	Sun L, Gilligan J, Staber C, Schutte R J, Nguyen V, O’Dowd D K, Reenan R (2012). A knock-in model of human epilepsy in Drosophila reveals a novel cellular mechanism associated with heat-induced seizure. J Neurosci, 32(41): 14145–14155 https://doi.org/10.1523/JNEUROSCI.2932-12.2012
113	Suzuki D, Grigliatti T, Williamson R (1971). Temperature-sensitive mutations in Drosophila melanogaster, VII. A mutation (parats) causing reversible adult paralysis. Proc Natl Acad Sci USA, 68(5): 890–893 https://doi.org/10.1073/pnas.68.5.890
114	Tan J S, Lin F, Tanouye M A (2004). Potassium bromide, an anticonvulsant, is effective at alleviating seizures in the Drosophila bang-sensitive mutant bang senseless. Brain Res, 1020(1-2): 45–52 https://doi.org/10.1016/j.brainres.2004.05.111
115	Tanouye M A, Ferrus A, Fujita S C (1981). Abnormal action potentials associated with the Shaker complex locus of Drosophila. Proc Natl Acad Sci USA, 78(10): 6548–6552 https://doi.org/10.1073/pnas.78.10.6548
116	Tao H, Manak J R, Sowers L, Mei X, Kiyonari H, Abe T, Dahdaleh N S, Yang T, Wu S, Chen S, Fox M H, Gurnett C, Montine T, Bird T, Shaffer L G, Rosenfeld J A, McConnell J, Madan-Khetarpal S, Berry-Kravis E, Griesbach H, Saneto R P, Scott M P, Antic D, Reed J, Boland R, Ehaideb S N, El-Shanti H, Mahajan V B, Ferguson P J, Axelrod J D, Lehesjoki A E, Fritzsch B, Slusarski D C, Wemmie J, Ueno N, Bassuk A G (2011). Mutations in Prickle orthologs cause seizures in flies, mice, and humans. Am J Hum Genet, 88(2): 138–149 https://doi.org/10.1016/j.ajhg.2010.12.012
117	Thackeray J R, Ganetzky B (1994). Developmentally regulated alternative splicing generates a complex array of Drosophila para sodium channel isoforms. J Neurosci, 14: 2569–2578
118	Thackeray J R, Ganetzky B (1995). Conserved alternative splicing patterns and splicing signals in the Drosophila sodium channel gene para. Genetics, 141: 203–214
119	Tornberg J, Voikar V, Savilahti H, Rauvala H, Airaksinen M S (2005). Behavioural phenotypes of hypomorphic KCC2-deficient mice. Eur J Neurosci, 21(5): 1327–1337 https://doi.org/10.1111/j.1460-9568.2005.03959.x
120	Ueda A, Grabbe C, Lee J, Lee J, Palmer R H, Wu C F (2008). Mutation of Drosophila focal adhesion kinase induces bang-sensitive behavior and disrupts glial function, axonal conduction and synaptic transmission. Eur J Neurosci, 27(11): 2860–2870 https://doi.org/10.1111/j.1460-9568.2008.06252.x
121	van der Bliek A M, Meyerowitz E M (1991). Dynamin-like protein encoded by the Drosophila shibire gene associated with vesicular traffic. Nature, 351(6325): 411–414 https://doi.org/10.1038/351411a0
122	Warmke J W, Reenan R A G, Wang P, Qian S, Arena J P, Wang J, Wunderler D, Liu K, Kaczorowski G J, Ploeg L H T V, Ganetzky B, Cohen C J (1997). Functional expression of Drosophila para sodium channels: modulation by the membrane protein tipE and toxin pharmacology. J Gen Physiol, 110(2): 119–133 https://doi.org/10.1085/jgp.110.2.119
123	Watanabe T K, Yamazaki T (1976). Evidence for coadaptation: negative correlation between lethal genes and polymorphic inversions in Drosophila melanogaster. Genetics, 82: 697–702
124	White H S, Smith M D, Wilcox K S (2007). Mechanisms of action of antiepileptic drugs. Int Rev Neurobiol, 81: 85–110 https://doi.org/10.1016/S0074-7742(06)81006-8
125	Willoughby L, Chang H, Lumb C, Robin C, Batterham P, Daborn P J (2006). A comparison of Drosophila melanogaster detoxification gene induction responses for six insecticides, caffeine and Phenobarbital. Insect Biochem Mol Biol, 36(12): 934–942 https://doi.org/10.1016/j.ibmb.2006.09.004
126	Woo N S, Lu J, England R, McClellan R, Dufour S, Mount D B, Deutch A Y, Lovinger D M, Delpire E (2002). Hyperexcitability and epilepsy associated with disruption of the mouse neuronal-specific K-Cl cotransporter gene. Hippocampus, 12(2): 258–268 https://doi.org/10.1002/hipo.10014
127	Wu C F, Ganetzky B (1980). Genetic alteration of nerve membrane excitability in temperature-sensitive paralytic mutants of Drosophila melanogaster. Nature, 286(5775): 814–816 https://doi.org/10.1038/286814a0
128	Zhang H, Tan J, Reynolds E, Kuebler D, Faulhaber S, Tanouye M A (2002). The Drosophila slamdance gene: a mutation in an aminopeptidase can cause seizure, paralysis and neuronal failure. Genetics, 162: 1283–1299
129	Zhang Y Q, Roote J, Brogna S, Davis A W, Barbash D A, Nash D, Ashburner M (1999). Stress sensitive B encodes an adenine nucleotide translocase in Drosophila melanogaster. Genetics, 153: 891–903
130	Zuckermann E C, Glaser G H (1970). Activation of experimental epileptogenic foci. Action of increased K+ in extracellular spaces of the brain. Arch Neurol, 23(4): 358–364 https://doi.org/10.1001/archneur.1970.00480280072008

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