Role of melatonin on calcium signaling and mitochondrial oxidativestress in epilepsy: focus on TRP channels

Calcium ion (Ca2+) accumulation and excessive oxidative stress in the hippocampus and brain cortex have long been known as major contributors to the etiology of epilepsy. I have reviewed the role of Ca2+ signaling through cation channels and mitochondria-mediated oxidative stress on epilepsy in human and animals. A review of the relevant papers and results from recent studies were obtained from PubMed and the Science Citation Index. Current literature findings indicate that melatonin and agomelatine reduce activation of hippocampal transient receptor potential (TRP), glutamate receptors, and voltage-gated calcium channels that are critical for the development of abnormal Ca2+ homeostasis and oxidative stress and associated mitochondrial dysfunction. In addition, low doses of melatonin induce anticonvulsant action through increase of GABA levels in the hippocampus and brain cortex. The accumulating evidence implicates a modulator role of melatonin on excessive oxidative stress products, plus mitochondrial and Ca2+ dysregulations in epilepsy. The evidence indicates that modulation of oxidative stress and neuronal Ca2+ handling occurs through effects on TRP channels, suggesting an increasingly viable approach for therapeutic interventions against epilepsy.

Anahtar Kelimeler:

Calcium ion, epilepsy, oxidative stress, melatonin, transient receptor potential channels, mitochondria

Role of melatonin on calcium signaling and mitochondrial oxidativestress in epilepsy: focus on TRP channels

Keywords:

Calcium ion, epilepsy, oxidative stress, melatonin, transient receptor potential channels, mitochondria,

PDF

___

Acuña Castroviejo D, Escames G, Carazo A, León J, Khaldy H, Reiter RJ (2002). Melatonin, mitochondrial homeostasis and mitochondrial-related diseases. Curr Top Med Chem 2: 133–151.
Aguiar CC, Almeida AB, Araújo PV, Vasconcelos GS, Chaves EM, do Vale OC, Macêdo DS, de Sousa FC, Viana GS, Vasconcelos SM (2012). Anticonvulsant effects of agomelatine in mice. Epilepsy Behav 24: 324–328.
Aguiar CC, Almeida AB, Araújo PV, Vasconcelos GS, Chaves EM, do Vale OC, Macêdo DS, Leal LK, de Barros Viana GS et al. (2013). Effects of agomelatine on oxidative stress in the brain of mice after chemically induced seizures. Cell Mol Neurobiol 33: 825–835.
Ahmed MA, Ahmed HI, El-Morsy EM (2013). Melatonin protects against diazinon-induced neurobehavioral changes in rats. Neurochem Res 38: 2227–2236.
Atanasova M, Petkova Z, Pechlivanova D, Dragomirova P, Blazhev A, Tchekalarova J (2013). Strain-dependent effects of longterm treatment with melatonin on kainic acid-induced status epilepticus, oxidative stress and the expression of heat shock proteins. Pharmacol Biochem Behav 111: 44–50.
Banach M, Gurdziel E, Jędrych M, Borowicz KK (2011). Melatonin in experimental seizures and epilepsy. Pharmacol Rep 63: 1–11.
Bejarano I, Espino J, González-Flores D, Casado JG, Redondo PC, Rosado JA, Barriga C, Pariente JA, Rodríguez AB (2009). Role of calcium signals on hydrogen peroxide-induced apoptosis in human myeloid HL-60 cells. Int J Biomed Sci 5: 246–256.
Bejarano I, Monllor F, Marchena AM, Ortiz A, Lozano G, Jimé- nez MI, Gaspar P, García JF, Pariente JA, Rodríguez AB et al. (2014). Exogenous melatonin supplementation prevents oxidative stress-evoked DNA damage in human spermatozoa. J Pineal Res 57: 333–339.
Bütün A, Nazıroğlu M, Demirci S, Çelik Ö, Uğuz AC (2015). Riboflavin and vitamin E increase brain calcium and antioxidants, and microsomal calcium-ATP-ase values in rat headache Models induced by glyceryl trinitrate. J Membr Biol 248: 205–213.
Cárdenas-Rodríguez N, Coballase-Urrutia E, Rivera-Espinosa L, Romero-Toledo A, Sampieri A 3rd, Ortega-Cuellar D, Montesinos-Correa H, Floriano-Sánchez E, Carmona-Aparicio L (2013). Modulation of antioxidant enzymatic activities by certain antiepileptic drugs (valproic acid, oxcarbazepine, and topiramate): evidence in humans and experimental models. Oxid Med Cell Longev 2013: 598493.
Celik O, Nazıroğlu M (2012). Melatonin modulates apoptosis and TRPM2 channels in transfected cells activated by oxidative stress. Physiol Behav 107: 458–465.
Choi TY, Kwon JE, Durrance ES, Jo SH, Choi SY, Kim KT (2014). Melatonin inhibits voltage-sensitive Ca(2+) channel-mediated neurotransmitter release. Brain Res 1557: 34–42.
Demirci S, Kutluhan S, Naziroğlu M, Uğuz AC, Yürekli VA, Demirci K (2013). Effects of selenium and topiramate on cytosolic Ca(2+) influx and oxidative stress in neuronal PC12 cells. Neurochem Res 38: 90–97.
Ekmekcioglu C (2006). Melatonin receptors in humans: biological role and clinical relevance. Biomed Pharm 60: 97–108.
Espino J, Bejarano I, Ortiz A, Lozano GM, García JF, Pariente JA, Rodríguez AB (2010). Melatonin as a potential tool against oxidative damage and apoptosis in ejaculated human spermatozoa. Fertil Steril 94: 1915–1917.
Espino J, Bejarano I, Paredes SD, Barriga C, Reiter RJ, Pariente JA, Rodríguez AB (2011a). Melatonin is able to delay endoplasmic reticulum stress-induced apoptosis in leukocytes from elderly humans. Age (Dordr) 33: 497–507.
Espino J, Bejarano I, Paredes SD, Barriga C, Rodríguez AB, Pariente JA (2011b). Protective effect of melatonin against human leukocyte apoptosis induced by intracellular calcium overload: relation with its antioxidant actions. J Pineal Res 51: 195–206.
Espino J, Pariente JA, Rodríguez AB (2012). Oxidative stress and immunosenescence: therapeutic effects of melatonin. Oxid Med Cell Longev 2012: 670294.
Esposito E, Cuzzocrea S (2010). Antiinflammatory activity of melatonin in central nervous system. Curr Neuropharmacol 8: 228–242.
Ghazizadeh V, Nazıroğlu M (2014). Electromagnetic radiation (WiFi) and epilepsy induce calcium entry and apoptosis through activation of TRPV1 channel in hippocampus and dorsal root ganglion of rats. Metab Brain Dis 29: 787–799.
Gupta S, Sharma B (2014). Pharmacological benefits of agomelatine and vanillin in experimental model of Huntington’s disease. Pharmacol Biochem Behav 122: 122–135.
Gustafsson G, Broström A, Ulander M, Vrethem M, Svanborg E (2015). Occurrence of epileptiform discharges and sleep during EEG recordings in children after melatonin intake versus sleep-deprivation. Clin Neurophysiol 126: 1493–1497.
Kim MH, Uehara S, Muroyama A, Hille B, Moriyama Y, Koh DS (2008). Glutamate transporter-mediated glutamate secretion in the mammalian pineal gland. J Neurosci 28: 10852–10863.
Kozai D, Ogawa N, Mori Y (2014). Redox regulation of transient receptor potential channels. Antioxid Redox Signal 21: 971–986.
Kumar VS, Gopalakrishnan A, Nazıroğlu M, Rajanikant GK (2014). Calcium ion--the key player in cerebral ischemia. Curr Med Chem 21: 2065–2075.
Kutluhan S, Naziroğlu M, Celik O, Yilmaz M (2009). Effects of selenium and topiramate on lipid peroxidation and antioxidant vitamin levels in blood of pentylentetrazol-induced epileptic rats. Biol Trace Elem Res 129: 181–189.
Lee SH, Chun W, Kong PJ, Han JA, Cho BP, Kwon OY, Lee HJ, Kim SS (2006). Sustained activation of Akt by melatonin contributes to the protection against kainic acid-induced neuronal death in hippocampus. J Pineal Res 40: 79–85.
Mareš J, Stopka P, Nohejlová K, Rokyta R (2013). Oxidative stress induced by epileptic seizure and its attenuation by melatonin. Physiol Res 62 (Suppl. 1): S67–74.
Martínez-Cruz F, Osuna C, Guerrero JM (2006). Mitochondrial damage induced by fetal hyperphenylalaninemia in the rat brain and liver: its prevention by melatonin, vitamin E, and vitamin C. Neurosci Lett 392: 1–4.
Méndez-Armenta M, Nava-Ruíz C, Juárez-Rebollar D, RodríguezMartínez E, Gómez PY (2014). Oxidative stress associated with neuronal apoptosis in experimental models of epilepsy. Oxid Med Cell Longev 2014: 293689.
Mohanan PV, Yamamoto HA (2002). Preventive effect of melatonin against brain mitochondria DNA damage, lipid peroxidation and seizures induced by kainic acid. Toxicol Lett 129: 99–105.
Molina-Carballo A, Acuña-Castroviejo D, Rodriguez-Cabezas T, Muñoz-Hoyos A (1994). Effects of febrile and epileptic convulsions on daily variations in plasma melatonin concentration in children. J Pineal Res 16: 1–9.
Molina-Carballo A, Muñoz-Hoyos A, Reiter RJ, Sánchez-Forte M, Moreno-Madrid F, Rufo-Campos M, Molina-Font JA, AcuñaCastroviejo D (1997). Utility of high doses of melatonin as adjunctive anticonvulsant therapy in a child with severe myoclonic epilepsy: two years’ experience. J Pineal Res 23: 97–105.
Molina-Carballo A, Muñoz-Hoyos A, Sánchez-Forte M, UberosFernández J, Moreno-Madrid F, Acuña-Castroviejo D (2007).
Melatonin increases following convulsive seizures may be related to its anticonvulsant properties at physiological concentrations. Neuropediatrics 38: 122–125.
Nazıroğlu M (2007). New molecular mechanisms on the activation of TRPM2 channels by oxidative stress and ADP-ribose. Neurochem Res 32: 1990–2001.
Nazıroğlu M (2009). Role of selenium on calcium signaling and oxidative stress-induced molecular pathways in epilepsy. Neurochem Res 34: 2181–2191.
Nazıroğlu M (2011). TRPM2 cation channels, oxidative stress and neurological diseases: where are we now? Neurochem Res 36: 355–366.
Nazıroğlu M (2012). Molecular role of catalase on oxidative stressinduced Ca(2+) signaling and TRP cation channel activation in nervous system. J Recept Signal Transduct Res 32: 134–141.
Nazıroğlu M (2015). TRPV1 channel: a potential drug target for treating epilepsy. Curr Neuropharmacol 13: 239–247.
Nazıroğlu M, Akay MB, Çelik Ö, Yıldırım Mİ, Balcı E, Yürekli VA (2013a). Capparis ovata modulates brain oxidative toxicity and epileptic seizures in pentylentetrazol-induced epileptic rats. Neurochem Res 38: 780–788.
Nazıroğlu M, Çelik Ö, Özgül C, Çiğ B, Doğan S, Bal R, Gümral N, Rodríguez AB, Pariente JA (2012a). Melatonin modulates wireless (2.45 GHz)-induced oxidative injury through TRPM2 and voltage gated Ca2+ channels in brain and dorsal root ganglion in rat. Physiol Behav 105: 683–692.
Nazıroğlu M, Demirdaş A (2015). Psychiatric disorders and TRP channels: focus on psychotropic drugs. Curr Neuropharmacol 13: 248–257.
Nazıroğlu M, Dikici DM, Dursun S (2012b). Role of oxidative stress and Ca2+ signaling on molecular pathways of neuropathic pain in diabetes: focus on TRP channels. Neurochem Res 37: 2065– 2075.
Nazıroğlu M, Kutluhan S, Uğuz AC, Celik O, Bal R, Butterworth PJ (2009). Topiramate and vitamin E modulate the electroencephalographic records, brain microsomal and blood antioxidant redox system in pentylentetrazol-induced seizure of rats. J Membr Biol 229: 131–140.
Nazıroğlu M, Kutluhan S, Yilmaz M (2008). Selenium and topiramate modulates brain microsomal oxidative stress values, Ca2+-ATPase activity, and EEG records in pentylentetrazolinduced seizures in rats. J Membr Biol 225: 39–49.
Nazıroğlu M, Övey IS (2015). Involvement of apoptosis and calcium accumulation through TRPV1 channels in neurobiology of epilepsy. Neuroscience 293: 55–66.
Nazıroğlu M, Özkan FF, Hapil SR, Ghazizadeh V, Çiğ B (2015). Epilepsy but not mobile phone frequency (900 MHz) induces apoptosis and calcium entry in hippocampus of epileptic rat: involvement of TRPV1 channels. J Membr Biol 248: 83–91.
Övey IS, Nazıroğlu M (2015). Homocysteine and cytosolic GSH depletion induce apoptosis and oxidative toxicity through cytosolic calcium overload in hippocampus of aged mice: involvement of TRPM2 and TRPV1 channels. Neuroscience 284C: 225–233.
Özmen I, Nazıroğlu M, Alicı HA, Sahin F, Cengiz M, Eren İ (2007). Spinal morphine administration reduces the fatty acid contents in spinal cord and brain in rabbits due to oxidative stress. Neurochem Res 32: 19–25.
Panda S, Nayak SK, Campo B, Walker JR, Hogenesch JB, Jegla T (2005). Illumination of the melanopsin signaling pathway. Science 307: 600–604.
Reuss S, Disque-Kaiser U, Binzen U, Greffrath W, Peschke E (2010). ‘TRPing’ synaptic ribbon function in the rat pineal gland: neuroendocrine regulation involves the capsaicin receptor TRPV1. Neuroendocrinology 92: 133–142.
Romá-Mateo C, Aguado C, García-Giménez JL, Knecht E, Sanz P, Pallardó FV (2015). Oxidative stress, a new hallmark in the pathophysiology of Lafora progressive myoclonus epilepsy. Free Radic Biol Med (in press).
Shenton FC, Pyner S (2014). Expression of transient receptor potential channels TRPC1 and TRPV4 in venoatrial endocardium of the rat heart. Neuroscience 267: 195–204.
Shorvon SD (2011). The etiologic classification of epilepsy. Epilepsia 52: 1052–1057.
Tchekalarova J, Petkova Z, Pechlivanova D, Moyanova S, Kortenska L, Mitreva R, Lozanov V, Atanasova D, Lazarov N, Stoynev A (2013). Prophylactic treatment with melatonin after status epilepticus: effects on epileptogenesis, neuronal damage, and behavioral changes in a kainate model of temporal lobe epilepsy. Epilepsy Behav 27: 174–187.
Tök L, Nazıroğlu M, Uğuz AC, Tök O (2014). Elevated hydrostatic pressures induce apoptosis and oxidative stress through mitochondrial membrane depolarization in PC12 neuronal cells: a cell culture model of glaucoma. J Recept Signal Transduct Res 34: 410–416.
Turgut M, Uyanikgil Y, Ateş U, Baka M, Yurtseven ME (2006). Pinealectomy stimulates and exogenous melatonin inhibits harmful effects of epileptiform activity during pregnancy in the hippocampus of newborn rats: an immunohistochemical study. Childs Nerv Syst 22: 481–488.
Vimala PV, Bhutada PS, Patel FR (2014). Therapeutic potential of agomelatine in epilepsy and epileptic complications. Med Hypotheses 82: 105–110.
Xu K, Stringer JL (2008). Antioxidants and free radical scavengers do not consistently delay seizure onset in animal models of acute seizures. Epilepsy Behav 13: 77–82.
Yalin O, Arman F, Erdoğan F, Kula M (2006). A comparison of the circadian rhythms and the levels of melatonin in patients with diurnal and nocturnal complex partial seizures. Epilepsy Behav 8: 542–546.
Yamamoto HA, Mohanan PV (2003). Ganglioside GT1B and melatonin inhibit brain mitochondrial DNA damage and seizures induced by kainic acid in mice. Brain Res 964: 100–106.
Yilmaz M, Nazıroğlu M, Kutluhan S, Yilmaz N, Yürekli VA, Vural H (2011). Topiramate modulates hippocampus NMDA receptors via brain Ca(2+) homeostasis in pentylentetrazol-induced epilepsy of rats. J Recept Signal Transduct Res 31: 173–179.
Yürekli VA, Nazıroğlu M (2013). Selenium and topiramate attenuates blood oxidative toxicity in patients with epilepsy: a clinical pilot study. Biol Trace Elem Res 152: 180–186.
Yürüker V, Nazıroğlu M, Şenol N (2015). Reduction in traumatic brain injury-induced oxidative stress, apoptosis, and calcium entry in rat hippocampus by melatonin: possible involvement of TRPM2 channels. Metab Brain Dis 30: 223–231.
Zhang E, Liao P (2015). Brain transient receptor potential channels and stroke. J Neurosci Res 93: 1165–1183.