Antiepileptogenic Effect of Retinoic Acid

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Abstract

Retinoic acid, a metabolite of vitamin A, acts through either genomic or nongenomic actions. The genomic action of retinoids exerts effects on gene transcription through interaction with retinoid receptors such as retinoic acid receptors (RARα, β, and γ) and retinoid X receptors (RXRα, β, and γ) that are primarily concentrated in the amygdala, pre-frontal cortex, and hippocampal areas in the brain. In response to retinoid binding, RAR/RXR heterodimers undergo major conformational changes and orchestrate the transcription of specific gene networks. Previous experimental studies have reported that retinoic acid exerts an antiepileptogenic effect through diverse mechanisms, including the modulation of gap junctions, neurotransmitters, long-term potentiation, calcium channels and some genes. To our knowledge, there are no previous or current clinical trials evaluating the use of retinoic acid for seizure control.

Keywords: Epilepsy, seizures, antiepileptic, retinoic acid, genes, retinoids.

Graphical Abstract

[1]
Sander, J.W. The Epidemiology of Epilepsy Revisited. Curr. Opin. Neurol., 2003, 16, 165-170.
[2]
Rudzinski, L.A.; Meador, K. J. Epilepsy: five new things. Neurology, 2011, 76(7)(Suppl. 2), S20-S25.
[http://dx.doi.org/10.1212/WNL.0b013e31820c3636] [PMID: 21321347]
[3]
de Oliveira, M.R. Vitamin A and retinoids as mitochondrial toxicants. Oxid. Med. Cell. Longev., 2015, 2015140267
[http://dx.doi.org/10.1155/2015/140267] [PMID: 26078802]
[4]
Tafti, M.; Ghyselinck, N.B. Functional implication of the vitamin A signaling pathway in the brain. Arch. Neurol., 2007, 64(12), 1706-1711.
[http://dx.doi.org/10.1001/archneur.64.12.1706] [PMID: 18071033]
[5]
Thorne-Lyman, A.; Fawzi, W.W.; Vitamin, D. Vitamin D during pregnancy and maternal, neonatal and infant health outcomes: a systematic review and meta-analysis. Paediatr. Perinat. Epidemiol., 2012, 26(Suppl. 1), 75-90.
[http://dx.doi.org/10.1111/j.1365-3016.2012.01283.x] [PMID: 22742603]
[6]
Huang, Z.; Liu, Y.; Qi, G.; Brand, D.; Zheng, S.G. Role of vitamin A in the immune system. J. Clin. Med., 2018, 7(9)E258
[http://dx.doi.org/10.3390/jcm7090258] [PMID: 30200565]
[7]
Yurdakok-Dikmen, B.; Filazi, A.; Ince, S. Retinoids; Reprod. Dev. Toxicol, 2017, pp. 481-492.
[8]
O’Byrne, S.M.; Blaner, W.S. Retinol and retinyl esters: biochemistry and physiology. J. Lipid Res., 2013, 54(7), 1731-1743.
[http://dx.doi.org/10.1194/jlr.R037648] [PMID: 23625372]
[9]
Al Tanoury, Z.; Piskunov, A.; Rochette-Egly, C. Vitamin A and retinoid signaling: genomic and nongenomic effects. J. Lipid Res., 2013, 54(7), 1761-1775.
[http://dx.doi.org/10.1194/jlr.R030833] [PMID: 23440512]
[10]
Napoli, J.L. Physiological insights into all-trans-retinoic acid biosynthesis. Biochim. Biophys. Acta, 2012, 1821(1), 152-167.
[http://dx.doi.org/10.1016/j.bbalip.2011.05.004] [PMID: 21621639]
[11]
McCaffery, P.; Lee, M.O.; Wagner, M.A.; Sladek, N.E.; Dräger, U.C. Asymmetrical retinoic acid synthesis in the dorsoventral axis of the retina. Development, 1992, 115(2), 371-382.
[PMID: 1425331]
[12]
Suzuki, R.; Shintani, T.; Sakuta, H.; Kato, A.; Ohkawara, T.; Osumi, N.; Noda, M. Identification of RALDH-3, a novel retinaldehyde dehydrogenase, expressed in the ventral region of the retina. Mech. Dev., 2000, 98(1-2), 37-50.
[http://dx.doi.org/10.1016/S0925-4773(00)00450-0] [PMID: 11044606]
[13]
Zhang, Y-R.; Zhao, Y-Q.; Huang, J-F. Retinoid-binding proteins: similar protein architectures bind similar ligands via completely different ways. PLoS One, 2012, 7(5)e36772
[http://dx.doi.org/10.1371/journal.pone.0036772] [PMID: 22574224]
[14]
Noy, N. Retinoid-binding proteins: mediators of retinoid action. Biochem. J., 2000, 348(Pt 3), 481-495.
[http://dx.doi.org/10.1042/bj3480481] [PMID: 10839978]
[15]
Moutier, E.; Ye, T.; Choukrallah, M.A.; Urban, S.; Osz, J.; Chatagnon, A.; Delacroix, L.; Langer, D.; Rochel, N.; Moras, D.; Benoit, G.; Davidson, I. Retinoic acid receptors recognize the mouse genome through binding elements with diverse spacing and topology. J. Biol. Chem., 2012, 287(31), 26328-26341.
[http://dx.doi.org/10.1074/jbc.M112.361790] [PMID: 22661711]
[16]
Bastien, J.; Rochette-Egly, C. Nuclear retinoid receptors and the transcription of retinoid-target genes. Gene, 2004, 328, 1-16.
[http://dx.doi.org/10.1016/j.gene.2003.12.005] [PMID: 15019979]
[17]
Durand, B.; Saunders, M.; Leroy, P.; Leid, M.; Chambon, P. All-trans and 9-cis retinoic acid induction of CRABPII transcription is mediated by RAR-RXR heterodimers bound to DR1 and DR2 repeated motifs. Cell, 1992, 71(1), 73-85.
[http://dx.doi.org/10.1016/0092-8674(92)90267-G] [PMID: 1327537]
[18]
Li, R.; Zhang, R.; Li, Y.; Zhu, B.; Chen, W.; Zhang, Y.; Chen, G. A RARE of hepatic Gck promoter interacts with RARα, HNF4α and COUP-TFII that affect retinoic acid- and insulin-induced Gck expression. J. Nutr. Biochem., 2014, 25(9), 964-976.
[http://dx.doi.org/10.1016/j.jnutbio.2014.04.009] [PMID: 24973045]
[19]
Brade, T.; Kumar, S.; Cunningham, T.J.; Chatzi, C.; Zhao, X.; Cavallero, S.; Li, P.; Sucov, H.M.; Ruiz-Lozano, P.; Duester, G. Retinoic acid stimulates myocardial expansion by induction of hepatic erythropoietin which activates epicardial Igf2. Development, 2011, 138(1), 139-148.
[http://dx.doi.org/10.1242/dev.054239] [PMID: 21138976]
[20]
Loudig, O.; Babichuk, C.; White, J.; Abu-Abed, S.; Mueller, C.; Petkovich, M. Cytochrome P450RAI(CYP26) promoter: a distinct composite retinoic acid response element underlies the complex regulation of retinoic acid metabolism. Mol. Endocrinol., 2000, 14(9), 1483-1497.
[http://dx.doi.org/10.1210/mend.14.9.0518] [PMID: 10976925]
[21]
Sucov, H.M.; Murakami, K.K.; Evans, R.M. Characterization of an autoregulated response element in the mouse retinoic acid receptor type β gene. Proc. Natl. Acad. Sci. USA, 1990, 87(14), 5392-5396.
[http://dx.doi.org/10.1073/pnas.87.14.5392] [PMID: 2164682]
[22]
Lee, C.H.; Wei, L.N. Characterization of an inverted repeat with a zero spacer (IR0)-type retinoic acid response element from the mouse nuclear orphan receptor TR2-11 gene. Biochemistry, 1999, 38(27), 8820-8825.
[http://dx.doi.org/10.1021/bi9903547] [PMID: 10393558]
[23]
Kobayashi, M.; Yu, R.T.; Yasuda, K.; Umesono, K. Cell-type-specific regulation of the retinoic acid receptor mediated by the orphan nuclear receptor TLX. Mol. Cell. Biol., 2000, 20(23), 8731-8739.
[http://dx.doi.org/10.1128/MCB.20.23.8731-8739.2000] [PMID: 11073974]
[24]
Ross, A.C. Retinoid production and catabolism: role of diet in regulating retinol esterification and retinoic Acid oxidation. J. Nutr., 2003, 133(1), 291S-296S.
[http://dx.doi.org/10.1093/jn/133.1.291S] [PMID: 12514312]
[25]
Dräger, U.C. Retinoic acid signaling in the functioning brain. Sci. STKE, 2006, 2006(324), pe10.
[http://dx.doi.org/10.1126/stke.3242006pe10] [PMID: 16507818]
[26]
Chen, L.; Lau, A.G.; Sarti, F. Synaptic retinoic acid signaling and homeostatic synaptic plasticity. Neuropharmacology, 2014, 78(C), 3-12.
[http://dx.doi.org/10.1016/j.neuropharm.2012.12.004] [PMID: 23270606]
[27]
Sarti, F.; Zhang, Z.; Schroeder, J.; Chen, L. Rapid suppression of inhibitory synaptic transmission by retinoic acid. J. Neurosci., 2013, 33(28), 11440-11450.
[http://dx.doi.org/10.1523/JNEUROSCI.1710-13.2013] [PMID: 23843516]
[28]
Ransom, J.; Morgan, P.J.; McCaffery, P.J.; Stoney, P.N. The rhythm of retinoids in the brain. J. Neurochem., 2014, 129(3), 366-376.
[http://dx.doi.org/10.1111/jnc.12620] [PMID: 24266881]
[29]
Zhang, D.Q.; McMahon, D.G. Direct gating by retinoic acid of retinal electrical synapses. Proc. Natl. Acad. Sci. USA, 2000, 97(26), 14754-14759.
[http://dx.doi.org/10.1073/pnas.010325897] [PMID: 11114157]
[30]
Weiler, R.; He, S.; Vaney, D.I. Retinoic acid modulates gap junctional permeability between horizontal cells of the mammalian retina. Eur. J. Neurosci., 1999, 11(9), 3346-3350.
[http://dx.doi.org/10.1046/j.1460-9568.1999.00799.x] [PMID: 10510200]
[31]
Zhang, D.; Vis, D. M.-M. undefined. Gating of retinal horizontal cell hemi gap junction channels by voltage, Ca2+, and retinoic acid. molvis.org.,. 2001.
[32]
Nielsen, M.S.; Axelsen, L.N.; Sorgen, P.L.; Verma, V.; Delmar, M.; Holstein-Rathlou, N-H. Gap junctions. Compr. Physiol., 2012, 2(3), 1981-2035.
[http://dx.doi.org/10.1002/cphy.c110051] [PMID: 23723031]
[33]
Falk, M.M. Biosynthesis and structural composition of gap junction intercellular membrane channels. Eur. J. Cell Biol., 2000, 79(8), 564-574.
[http://dx.doi.org/10.1078/0171-9335-00080] [PMID: 11001493]
[34]
Bennett, M.V.; Goodenough, D.A. Gap junctions, electrotonic coupling, and intercellular communication. Neurosci. Res. Program Bull., 1978, 16(3), 1-486.
[PMID: 216953]
[35]
Simon, A.M.; Goodenough, D.A. Diverse functions of vertebrate gap junctions. Trends Cell Biol., 1998, 8(12), 477-483.
[http://dx.doi.org/10.1016/S0962-8924(98)01372-5] [PMID: 9861669]
[36]
Mammano, F. Gap Junctions: Cell-Cell Channels in Animals.,, 2013.
[37]
Mylvaganam, S.; Ramani, M.; Krawczyk, M.; Carlen, P.L. Roles of gap junctions, connexins, and pannexins in epilepsy. Front. Physiol., 2014, 5, 172.
[http://dx.doi.org/10.3389/fphys.2014.00172] [PMID: 24847276]
[38]
Jin, M-M.; Chen, Z. Role of gap junctions in epilepsy. Neurosci. Bull., 2011, 27(6), 389-406.
[http://dx.doi.org/10.1007/s12264-011-1944-1] [PMID: 22108816]
[39]
Juszczak, G.R.; Swiergiel, A.H. Properties of gap junction blockers and their behavioural, cognitive and electrophysiological effects: animal and human studies. Prog. Neuropsychopharmacol. Biol. Psychiatry, 2009, 33(2), 181-198.
[http://dx.doi.org/10.1016/j.pnpbp.2008.12.014] [PMID: 19162118]
[40]
Li, Q.; Li, Q.Q.; Jia, J.N.; Liu, Z.Q.; Zhou, H.H.; Mao, X.Y. Targeting gap junction in epilepsy: Perspectives and challenges. Biomed. Pharmacother., 2019, 109(109), 57-65.
[http://dx.doi.org/10.1016/j.biopha.2018.10.068] [PMID: 30396092]
[41]
Gajda, Z.; Gyengési, E.; Hermesz, E.; Ali, K.S.; Szente, M. Involvement of gap junctions in the manifestation and control of the duration of seizures in rats in vivo. Epilepsia, 2003, 44(12), 1596-1600.
[http://dx.doi.org/10.1111/j.0013-9580.2003.25803.x] [PMID: 14636335]
[42]
Sayyah, M.; Rezaie, M.; Haghighi, S.; Amanzadeh, A. Intra-amygdala all-trans retinoic acid inhibits amygdala-kindled seizures in rats. Epilepsy Res., 2007, 75(2-3), 97-103.
[http://dx.doi.org/10.1016/j.eplepsyres.2007.04.010] [PMID: 17553672]
[43]
Yang, Y.; Qin, S.K.; Wu, Q.; Wang, Z.S.; Zheng, R.S.; Tong, X.H.; Liu, H.; Tao, L.; He, X.D. Connexin-dependent gap junction enhancement is involved in the synergistic effect of sorafenib and all-trans retinoic acid on HCC growth inhibition. Oncol. Rep., 2014, 31(2), 540-550.
[http://dx.doi.org/10.3892/or.2013.2894] [PMID: 24317203]
[44]
Long, A.C.; Bomser, J.A.; Grzybowski, D.M.; Chandler, H.L. All-trans retinoic Acid regulates cx43 expression, gap junction communication and differentiation in primary lens epithelial cells. Curr. Eye Res., 2010, 35(8), 670-679.
[http://dx.doi.org/10.3109/02713681003770746] [PMID: 20673043]
[45]
Maret, S.; Franken, P.; Dauvilliers, Y.; Ghyselinck, N. B.; Chambon, P.; Tafti, M. Retinoic acid signaling affects cortical synchrony during sleep. Science (80-.)., 2005, 310(5745), 111-113.,
[http://dx.doi.org/10.1126/science.1117623.]
[46]
Kitaoka, K.; Hattori, A.; Chikahisa, S.; Miyamoto, K.; Nakaya, Y.; Sei, H. Vitamin A deficiency induces a decrease in EEG delta power during sleep in mice. Brain Res., 2007, 1150(1), 121-130.
[http://dx.doi.org/10.1016/j.brainres.2007.02.077] [PMID: 17400199]
[47]
Kitaoka, K.; Shimizu, M.; Shimizu, N.; Chikahisa, S.; Nakagomi, M.; Shudo, K.; Yoshizaki, K.; Séi, H. Retinoic acid receptor antagonist LE540 attenuates wakefulness via the dopamine D1 receptor in mice. Brain Res., 2011, 1423, 10-16.
[http://dx.doi.org/10.1016/j.brainres.2011.09.023] [PMID: 22000589]
[48]
Cooke, S.F.; Bliss, T.V.P. Plasticity in the Human Central Nervous System. Brain; Oxford University Press, 2006, pp. 1659-1673.
[49]
Meador, K.J. The Basic Science of Memory as It Applies to Epilepsy.Epilepsia; John Wiley & Sons. Ltd, 2007Vol. 48, pp. , 23-25.
[http://dx.doi.org/10.1111/j.1528-1167.2007.01396.x]
[50]
Ben-Ari, Y.; Represa, A. Brief seizure episodes induce long-term potentiation and mossy fibre sprouting in the hippocampus. Trends Neurosci., 1990, 13(8), 312-318.
[http://dx.doi.org/10.1016/0166-2236(90)90135-W] [PMID: 1699312]
[51]
Reid, I.C.; Stewart, C.A. Seizures, memory and synaptic plasticity. Seizure, 1997, 6(5), 351-359.
[http://dx.doi.org/10.1016/S1059-1311(97)80034-9] [PMID: 9663798]
[52]
Arendt, K.L.; Zhang, Y.; Jurado, S.; Malenka, R.C.; Südhof, T.C.; Chen, L. Retinoic acid and LTP recruit postsynaptic AMPA receptors using distinct SNARE-dependent mechanisms. Neuron, 2015, 86(2), 442-456.
[http://dx.doi.org/10.1016/j.neuron.2015.03.009] [PMID: 25843403]
[53]
Chiang, M.Y.; Misner, D.; Kempermann, G.; Schikorski, T.; Giguère, V.; Sucov, H.M.; Gage, F.H.; Stevens, C.F.; Evans, R.M. An essential role for retinoid receptors RARbeta and RXRgamma in long-term potentiation and depression. Neuron, 1998, 21(6), 1353-1361.
[http://dx.doi.org/10.1016/S0896-6273(00)80654-6] [PMID: 9883728]
[54]
de Hoog, E.; Lukewich, M.K.; Spencer, G.E. Retinoic acid inhibits neuronal voltage-gated calcium channels. Cell Calcium, 2018, 72, 51-61.
[http://dx.doi.org/10.1016/j.ceca.2018.02.001] [PMID: 29748133]
[55]
de Hoog, E.; Lukewich, M.K.; Spencer, G.E. Retinoid receptor-based signaling plays a role in voltage-dependent inhibition of invertebrate voltage-gated Ca2+ channels. J. Biol. Chem., 2019, 294(26), 10076-10093.
[http://dx.doi.org/10.1074/jbc.RA118.006444] [PMID: 31048374]
[56]
Jiang, W.; Yu, Q.; Gong, M.; Chen, L.; Wen, E.Y.; Bi, Y.; Zhang, Y.; Shi, Y.; Qu, P.; Liu, Y.X.; Wei, X.P.; Chen, J.; Li, T.Y. Vitamin A deficiency impairs postnatal cognitive function via inhibition of neuronal calcium excitability in hippocampus. J. Neurochem., 2012, 121(6), 932-943.
[http://dx.doi.org/10.1111/j.1471-4159.2012.07697.x] [PMID: 22352986]
[57]
Gao, Z.Y.; Xu, G.; Stwora-Wojczyk, M.M.; Matschinsky, F.M.; Lee, V.M.Y.; Wolf, B.A. Retinoic acid induction of calcium channel expression in human NT2N neurons. Biochem. Biophys. Res. Commun., 1998, 247(2), 407-413.
[http://dx.doi.org/10.1006/bbrc.1998.8826] [PMID: 9642141]
[58]
Zhong, L.R.; Chen, X.; Park, E.; Südhof, T.C.; Chen, L. Retinoic Acid receptor RARα-dependent synaptic signaling mediates homeostatic synaptic plasticity at the inhibitory synapses of mouse visual cortex. J. Neurosci., 2018, 38(49), 10454-10466.
[http://dx.doi.org/10.1523/JNEUROSCI.1133-18.2018] [PMID: 30355624]
[59]
Steinlein, O.K. Genetic mechanisms that underlie epilepsy. Nat. Rev. Neurosci., 2004, 5(5), 400-408.
[http://dx.doi.org/10.1038/nrn1388] [PMID: 15100722]
[60]
Steinlein, O.K. Genes and mutations in human idiopathic epilepsy. Brain Dev., 2004, 26(4), 213-218.
[http://dx.doi.org/10.1016/S0387-7604(03)00149-9] [PMID: 15130686]
[61]
Mantegazza, M.; Rusconi, R.; Cestèle, S. Mutations of ion channels in genetic epilepsies. Epilepsy Towards the Next Decade; Springer International Publishing: Cham, 2015, pp. 15-34.
[http://dx.doi.org/10.1007/978-3-319-12283-0_2]
[62]
Scheffer, I.E.; Berkovic, S.F. The genetics of human epilepsy. Trends Pharmacol. Sci., 2003, 24(8), 428-433.
[http://dx.doi.org/10.1016/S0165-6147(03)00194-9] [PMID: 12915053]
[63]
Li, Y.; Shan, X.; Wu, Z.; Wang, Y.; Ling, M.; Fan, X. idh1 mutation is associated with a higher preoperative seizure incidence in low-grade glioma: a systematic review and meta-analysis. Seizure; W.B. Saunders Ltd, 2018..
[http://dx.doi.org/10.1016/j.seizure.2018.01.011.]
[64]
Bender, R.A.; Baram, T.Z. Epileptogenesis in the developing brain: what can we learn from animal models? Epilepsia, 2007, 48(Suppl. 5), 2-6.
[http://dx.doi.org/10.1111/j.1528-1167.2007.01281.x] [PMID: 17910574]
[65]
Pramparo, T.; Grosso, S.; Messa, J.; Zatterale, A.; Bonaglia, M.C.; Chessa, L.; Balestri, P.; Rocchi, M.; Zuffardi, O.; Giorda, R. Loss-of-function mutation of the AF9/MLLT3 gene in a girl with neuromotor development delay, cerebellar ataxia, and epilepsy. Hum. Genet., 2005, 118(1), 76-81.
[http://dx.doi.org/10.1007/s00439-005-0004-1] [PMID: 16001262]
[66]
Subashini, C.; Dhanesh, S.B.; Chen, C.M.; Riya, P.A.; Meera, V.; Divya, T.S.; Kuruvilla, R.; Buttler, K.; James, J. Wnt5a is a crucial regulator of neurogenesis during cerebellum development. Sci. Rep., 2017, 7, 42523.
[http://dx.doi.org/10.1038/srep42523] [PMID: 28205531]
[67]
Theilhaber, J.; Rakhade, S.N.; Sudhalter, J.; Kothari, N.; Klein, P.; Pollard, J.; Jensen, F.E. Gene expression profiling of a hypoxic seizure model of epilepsy suggests a role for mTOR and Wnt signaling in epileptogenesis. PLoS One, 2013, 8(9)e74428
[http://dx.doi.org/10.1371/journal.pone.0074428] [PMID: 24086344]
[68]
O’Donnell-Luria, A.H.; Pais, L.S.; Faundes, V.; Wood, J.C.; Sveden, A.; Luria, V.; Abou, J.R.; Accogli, A.; Amburgey, K.; Anderlid, B.M.; Azzarello-Burri, S.; Basinger, A.A.; Bianchini, C.; Bird, L.M.; Buchert, R.; Carre, W.; Ceulemans, S.; Charles, P.; Cox, H.; Culliton, L.; Currò, A.; Demurger, F.; Dowling, J.J.; Duban-Bedu, B.; Dubourg, C.; Eiset, S.E.; Escobar, L.F.; Ferrarini, A.; Haack, T.B.; Hashim, M.; Heide, S.; Helbig, K.L.; Helbig, I.; Heredia, R.; Héron, D.; Isidor, B.; Jonasson, A.R.; Joset, P.; Keren, B.; Kok, F.; Kroes, H.Y.; Lavillaureix, A.; Lu, X.; Maas, S.M.; Maegawa, G.H.B.; Marcelis, C.L.M.; Mark, P.R.; Masruha, M.R.; McLaughlin, H.M.; McWalter, K.; Melchinger, E.U.; Mercimek-Andrews, S.; Nava, C.; Pendziwiat, M.; Person, R.; Ramelli, G.P.; Ramos, L.L.P.; Rauch, A.; Reavey, C.; Renieri, A.; Rieß, A.; Sanchez-Valle, A.; Sattar, S.; Saunders, C.; Schwarz, N.; Smol, T.; Srour, M.; Steindl, K.; Syrbe, S.; Taylor, J.C.; Telegrafi, A.; Thiffault, I.; Trauner, D.A.; van der Linden, H., Jr; van Koningsbruggen, S.; Villard, L.; Vogel, I.; Vogt, J.; Weber, Y.G.; Wentzensen, I.M.; Widjaja, E.; Zak, J.; Baxter, S.; Banka, S.; Rodan, L.H. Deciphering Developmental Disorders (DDD) Study. Heterozygous variants in KMT2E cause a spectrum of neurodevelopmental disorders and epilepsy. Am. J. Hum. Genet., 2019, 104(6), 1210-1222.
[http://dx.doi.org/10.1016/j.ajhg.2019.03.021] [PMID: 31079897]
[69]
Hu, X.; Fu, X.; Jiang, A.O.; Yang, X.; Fang, X.; Gong, G.; Wei, C. Multiomic analysis of mice epilepsy models suggest that miR-21a expression modulates mRNA and protein levels related to seizure deterioration. Genet. Res., 2015, 97e22
[http://dx.doi.org/10.1017/S0016672315000245] [PMID: 26689812]
[70]
Pardo, B.; Contreras, L.; Satrústegui, J. De novo synthesis of glial glutamate and glutamine in young mice requires aspartate provided by the neuronal mitochondrial aspartate-glutamate carrier Aralar/AGC1. Front. Endocrinol. (Lausanne), 2013, 4, 149.
[http://dx.doi.org/10.3389/fendo.2013.00149] [PMID: 24133485]
[72]
Mirzaa, G.; Parry, D.A.; Fry, A.E.; Giamanco, K.A.; Schwartzentruber, J.; Vanstone, M.; Logan, C.V.; Roberts, N.; Johnson, C.A.; Singh, S.; Kholmanskikh, S.S.; Adams, C.; Hodge, R.D.; Hevner, R.F.; Bonthron, D.T.; Braun, K.P.J.; Faivre, L.; Rivière, J.B.; St-Onge, J.; Gripp, K.W.; Mancini, G.M.; Pang, K.; Sweeney, E.; van Esch, H.; Verbeek, N.; Wieczorek, D.; Steinraths, M.; Majewski, J.; Boycot, K.M.; Pilz, D.T.; Ross, M.E.; Dobyns, W.B.; Sheridan, E.G. FORGE Canada Consortium.De novo CCND2 mutations leading to stabilization of cyclin D2 cause megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome. Nat. Genet., 2014, 46(5), 510-515.
[http://dx.doi.org/10.1038/ng.2948] [PMID: 24705253]
[73]
[74]
Cox, A.J.; Grady, F.; Velez, G.; Mahajan, V.B.; Ferguson, P.J.; Kitchen, A.; Darbro, B.W.; Bassuk, A.G. In trans variant calling reveals enrichment for compound heterozygous variants in genes involved in neuronal development and growth. Genet. Res., 2019, 101,e8.
[http://dx.doi.org/10.1017/S0016672319000065] [PMID: 31190668]
[75]
Klassen, H.J. Neural flow cytometry - a historical account from a personal perspective.neural surface antigens: From basic biology towards biomedical applications; Elsevier Inc., 2015, pp. 167-173.
[http://dx.doi.org/10.1016/B978-0-12-800781-5.00014-1]
[76]
Fabene, P.F.; Navarro Mora, G.; Martinello, M.; Rossi, B.; Merigo, F.; Ottoboni, L.; Bach, S.; Angiari, S.; Benati, D.; Chakir, A.; Zanetti, L.; Schio, F.; Osculati, A.; Marzola, P.; Nicolato, E.; Homeister, J.W.; Xia, L.; Lowe, J.B.; McEver, R.P.; Osculati, F.; Sbarbati, A.; Butcher, E.C.; Constantin, G. A role for leukocyte-endothelial adhesion mechanisms in epilepsy. Nat. Med., 2008, 14(12), 1377-1383.
[http://dx.doi.org/10.1038/nm.1878] [PMID: 19029985]
[77]
Vaidya, V.A.; Lakhina, V.; Subramanian, L.; Huilgol, D.; Shetty, A.S.; Tole, S. Seizure evoked regulation of LIM-HD genes and co-factors in the postnatal and adult hippocampus. F1000 Res., 2013, 2.
[http://dx.doi.org/10.12688/f1000research.2-205.v1]
[78]
Nakashima, M.; Tohyama, J.; Nakagawa, E.; Watanabe, Y.; Siew, C.G.; Kwong, C.S.; Yamoto, K.; Hiraide, T.; Fukuda, T.; Kaname, T.; Nakabayashi, K.; Hata, K.; Ogata, T.; Saitsu, H.; Matsumoto, N. Identification of de novo CSNK2A1 and CSNK2B variants in cases of global developmental delay with seizures. J. Hum. Genet., 2019, 64(4), 313-322.
[http://dx.doi.org/10.1038/s10038-018-0559-z] [PMID: 30655572]
[79]
Grimaldi, G.; Vagaska, B.; Ievglevskyi, O.; Kondratskaya, E.; Glover, J.; Matthews, J. Loss of tiparp results in aberrant layering of the cerebral cortex. eneuro. eNeuro, 2019ENEURO. 0239. , 19.
[http://dx.doi.org/10.1523/ENEURO.0239-19.2019.]
[80]
Fajardo, M.; Cirillo, M.L. Understanding the spectrum of SLC2A1-associated disorders. Pediatr. Neurol. Briefs, 2017, 31(2), 4.
[http://dx.doi.org/10.15844/pedneurbriefs-31-2-1] [PMID: 28507422]
[81]
Mirzaa, G. ]MPPH Syndrome, In gene reviews [internet]. Seattle (WA): University of Washington, Seattle 1993-2020.,
[82]
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. A homozygous mutation in human PRICKLE1 causes an autosomal-recessive progressive myoclonus epilepsy-ataxia syndrome. Am. J. Hum. Genet., 2008, 83(5), 572-581.
[http://dx.doi.org/10.1016/j.ajhg.2008.10.003] [PMID: 18976727]
[83]
Rudolf, G.; Lesca, G.; Mehrjouy, M.M.; Labalme, A.; Salmi, M.; Bache, I.; Bruneau, N.; Pendziwiat, M.; Fluss, J.; de Bellescize, J.; Scholly, J.; Møller, R.S.; Craiu, D.; Tommerup, N.; Valenti-Hirsch, M.P.; Schluth-Bolard, C.; Sloan-Béna, F.; Helbig, K.L.; Weckhuysen, S.; Edery, P.; Coulbaut, S.; Abbas, M.; Scheffer, I.E.; Tang, S.; Myers, C.T.; Stamberger, H.; Carvill, G.L.; Shinde, D.N.; Mefford, H.C.; Neagu, E.; Huether, R.; Lu, H.M.; Dica, A.; Cohen, J.S.; Iliescu, C.; Pomeran, C.; Rubenstein, J.; Helbig, I.; Sanlaville, D.; Hirsch, E.; Szepetowski, P. Loss of function of the retinoid-related nuclear receptor (RORB) gene and epilepsy. Eur. J. Hum. Genet., 2016, 24(12), 1761-1770.
[http://dx.doi.org/10.1038/ejhg.2016.80] [PMID: 27352968]
[84]
Baglietto, M.G.; Caridi, G.; Gimelli, G.; Mancardi, M.; Prato, G.; Ronchetto, P.; Cuoco, C.; Tassano, E. RORB gene and 9q21.13 microdeletion: report on a patient with epilepsy and mild intellectual disability. Eur. J. Med. Genet., 2014, 57(1), 44-46.
[http://dx.doi.org/10.1016/j.ejmg.2013.12.001] [PMID: 24355400]
[85]
Lee, C.G.; Park, S-J.; Yun, J-N.; Yim, S-Y.; Sohn, Y.B. Reciprocal deletion and duplication of 17p11.2-11.2: Korean patients with Smith-Magenis syndrome and Potocki-Lupski syndrome. J. Korean Med. Sci., 2012, 27(12), 1586-1590.
[http://dx.doi.org/10.3346/jkms.2012.27.12.1586] [PMID: 23255863]
[86]
Toulouse, A.; Rochefort, D.; Roussel, J.; Joober, R.; Rouleau, G.A. Molecular cloning and characterization of human RAI1, a gene associated with schizophrenia. Genomics, 2003, 82(2), 162-171.
[http://dx.doi.org/10.1016/S0888-7543(03)00101-0] [PMID: 12837267]
[87]
Vilboux, T.; Ciccone, C.; Blancato, J.K.; Cox, G.F.; Deshpande, C.; Introne, W.J.; Gahl, W.A.; Smith, A.C.M.; Huizing, M. Molecular analysis of the Retinoic Acid Induced 1 gene (RAI1) in patients with suspected Smith-Magenis syndrome without the 17p11.2 deletion. PLoS One, 2011, 6(8)e22861
[http://dx.doi.org/10.1371/journal.pone.0022861] [PMID: 21857958]
[88]
Carmona-Mora, P.; Walz, K. Retinoic acid induced 1, RAI1: A dosage sensitive gene related to neurobehavioral alterations including autistic behavior. Curr. Genomics, 2010, 11(8), 607-617.
[http://dx.doi.org/10.2174/138920210793360952] [PMID: 21629438]
[89]
Fujieda, H.; Bremner, R.; Mears, A.J.; Sasaki, H. Retinoic acid receptor-related orphan receptor α regulates a subset of cone genes during mouse retinal development. J. Neurochem., 2009, 108(1), 91-101.
[http://dx.doi.org/10.1111/j.1471-4159.2008.05739.x] [PMID: 19014374]
[90]
Jetten, A.M. Retinoid-Related Orphan Receptors (RORs): Critical Roles in Development, Immunity, Circadian Rhythm, and Cellular Metabolism. Nuclear receptor signaling; SAGE Publications, 2009.
[91]
Guissart, C.; Latypova, X.; Rollier, P.; Khan, T.N.; Stamberger, H.; McWalter, K.; Cho, M.T.; Kjaergaard, S.; Weckhuysen, S.; Lesca, G.; Besnard, T.; Õunap, K.; Schema, L.; Chiocchetti, A.G.; McDonald, M.; de Bellescize, J.; Vincent, M.; Van Esch, H.; Sattler, S.; Forghani, I.; Thiffault, I.; Freitag, C.M.; Barbouth, D.S.; Cadieux-Dion, M.; Willaert, R.; Guillen Sacoto, M.J.; Safina, N.P.; Dubourg, C.; Grote, L.; Carré, W.; Saunders, C.; Pajusalu, S.; Farrow, E.; Boland, A.; Karlowicz, D.H.; Deleuze, J.F.; Wojcik, M.H.; Pressman, R.; Isidor, B.; Vogels, A.; Van Paesschen, W.; Al-Gazali, L.; Al Shamsi, A.M.; Claustres, M.; Pujol, A.; Sanders, S.J.; Rivier, F.; Leboucq, N.; Cogné, B.; Sasorith, S.; Sanlaville, D.; Retterer, K.; Odent, S.; Katsanis, N.; Bézieau, S.; Koenig, M.; Davis, E.E.; Pasquier, L.; Küry, S. Dual molecular effects of dominant RORA mutations cause two variants of syndromic intellectual disability with either autism or cerebellar ataxia. Am. J. Hum. Genet., 2018, 102(5), 744-759.
[http://dx.doi.org/10.1016/j.ajhg.2018.02.021] [PMID: 29656859]