Russian Journal of Biological Physics and Chemisrty Russian Journal of Biological Physics and Chemisrty АКТУАЛЬНЫЕ ВОПРОСЫ БИОЛОГИЧЕСКОЙ ФИЗИКИ И ХИМИИ 2499-9962 54685 МЕДИЦИНСКАЯ БИОФИЗИКА И БИОФИЗИЧЕСКАЯ ХИМИЯ MEDICAL BIOPHYSICS AND BIOPHYSICAL CHEMISTRY МЕДИЦИНСКАЯ БИОФИЗИКА И БИОФИЗИЧЕСКАЯ ХИМИЯ Membrane contamination hypothesis for epileptic activity Гипотеза контаминации мембран при эпилепсии Нечипуренко Ю Д Nechipurenko Yu D nech99@mail.ru Касерес Х Л Hernandez Caceres J L Институт молекулярной биологии им. В.А. Энгельгардта РАН ru Engelhardt Institute of Molecular Biology, Russian Academy of Sciences ru Cuban Neurosciences Center ru Cuban Center for Neurosciences ru 25 09 2021 25 09 2021 6 3 520 524 20 09 2021 20 09 2021 https://rusjbpc.ru/en/nauka/article/54685/view

Приводятся данные в пользу гипотезы Альтрупа о контаминации мембраны, связывающей пароксизмальную деполяризацию, наблюдаемую при эпилептической активности, с пейсмекерным потенциалом. Предложена связь между физико-химическими характеристиками мембраны, текучестью и контаминациями, и способностью проводить импульс и перезаряжаться. Обсуждаются предложенные ранее способы лечения эпилепсии, основанные на кетогенной диете и их возможные механизмы в свете гипотезы Альтрупа. Среди возможных механизмов действия кетогенной диеты подчеркивается противоэпилептическое действие кетоновых тел, роль повышенного синтеза глутатиона и эффект полиненасыщенных жирных кислот и холестерина, включенных в состав диеты. Эти три механизма, среди других эффектов, приводят к регуляции текучести и других биофизических свойств липидного бислоя, а также к очищению мембраны от амфифильных примесей.

Evidences are provided supporting Altrup’s membrane pollution hypothesis that links paroxysmal depolarization shifts observed during epileptic activity, and pacemaker potentials. It is proposed a connection between membrane’s physic-chemical characteristics, fluidity and pollution with neuron’s ability to conduct impulses during excitation. There are discussed previously used means of epilepsy treatment based on the ketogenic diet, as well as their possible mechanisms on the light of Altrup’s hypothesis. Among possible mechanisms for ketogenic diet, we underline ketone bodies antiepileptic actionthe role of increased synthesis of glutathione as well as the role played by polyunsaturated fatty acids (PUFA) and cholesterol as components included into the ketogenic diet. These three mechanisms, among others, lead to a regulation of fluidity and other biophysical properties of the membrane bilayer as well as to a cleansing of the membrane from amphiphilic polluters, in accordance with Altrup’s hypothesis.

 эпилептическая активность пароксизмальная деполяризация пейсмекерный потенциал гипотеза Альтрупа контаминация мембран латеральное давление мембран кетогенная диета глутатион Epileptic activity paroxysmal depolarization shifts pacemaker potential Altrup’s hypothesis membrane pollution lateral pressure ketogenic diet glutathione Работа выполнена при поддержке Кубинского Научного Фонда (FONCI), Проект Нефармакологической Антиэпилептической Терапии, координируемый Кубинским Центром Нейронаук а также финансовой поддержке Программы фундаментальных исследований государственных академий наук России на 2013-2020 годы (темы №01201363818 и № 01201363820).

Walden J., Straub H., Speckmann E.J. Epileptogenesis: contributions of calcium ions and antiepileptic calcium antagonists. Acta neurologica Scandinavica. Supplementum, 1992, vol. 140, pp. 41-46. Walden J., Straub H., Speckmann E.J. Epileptogenesis: contributions of calcium ions and antiepileptic calcium antagonists. Acta neurologica Scandinavica. Supplementum, 1992, vol. 140, pp. 41-46. Engelborghs S., D’Hooge R., De Deyn P.P. Pathophysiology of epilepsy. Acta Neurol. Belg., 2000, vol. 100, pp. 201-213. Engelborghs S., D’Hooge R., De Deyn P.P. Pathophysiology of epilepsy. Acta Neurol. Belg., 2000, vol. 100, pp. 201-213. Altrup U., Hader M., Hernandez Caceres J.L., Malcharek S., Meyer M., Galla H.-J. Epileptogenic drugs in a model nervous system: Electrophysiological effects and incorporation into a phospholipid layer. Brain Research, 2006, vol. 1122, pp. 65-77. Altrup U., Hader M., Hernandez Caceres J.L., Malcharek S., Meyer M., Galla H.-J. Epileptogenic drugs in a model nervous system: Electrophysiological effects and incorporation into a phospholipid layer. Brain Research, 2006, vol. 1122, pp. 65-77. Wiemann M., Wittkowski W., Altrup U., Speckmann E.-J., Alterations of neuronal fibers after epileptic activity induced by pentylenetetrazol: fine structure investigated by calcium cytochemistry and neurobiotin labeling (buccal ganglia, Helix pomatia). Cell Tissue Res, vol. 996, no. 286, pp. 43-53; Wiemann M., Wittkowski W., Altrup U., Speckmann E.-J., Alterations of neuronal fibers after epileptic activity induced by pentylenetetrazol: fine structure investigated by calcium cytochemistry and neurobiotin labeling (buccal ganglia, Helix pomatia). Cell Tissue Res, vol. 996, no. 286, pp. 43-53; Speckmann E.-J., Caspers H. Paroxysmal depolarization induced by pentylenetetrazol in isolated neurons of Helix pomatia. Epilepsia, 1973, vol. 14, pp. 397-408. Speckmann E.-J., Caspers H. Paroxysmal depolarization induced by pentylenetetrazol in isolated neurons of Helix pomatia. Epilepsia, 1973, vol. 14, pp. 397-408. Segal M. Epileptiform activity in microcultures containing one hippocampal neuron. J. Neurophysiol, 1991, vol. 65, pp. 761-770. Segal M. Epileptiform activity in microcultures containing one hippocampal neuron. J. Neurophysiol, 1991, vol. 65, pp. 761-770. Никитин Е.С., Балабан П.М. Структурно-функциональная организация сети серотонинэргических нейронов наземной улитки. Журнал высшей нервной деятельности им. И.П.Павлова, 2011, vol. 61, no. 6, pp. 750-762. @@Nikitin E.S., Balaban P.M. Structural and functional organization of the network of serotoninergic neurons of the land snail. Journal of Higher Nervous Activity named after I. P. Pavlov, 2011, vol. 61, no. 6, pp. 750-762. (In Russ.) Nikitin E.S., Balaban P.M. Strukturno-funkcional'naya organizaciya seti serotoninergicheskih neyronov nazemnoy ulitki. Zhurnal vysshey nervnoy deyatel'nosti im. I.P.Pavlova, 2011, vol. 61, no. 6, pp. 750-762. @@Nikitin E.S., Balaban P.M. Structural and functional organization of the network of serotoninergic neurons of the land snail. Journal of Higher Nervous Activity named after I. P. Pavlov, 2011, vol. 61, no. 6, pp. 750-762. (In Russ.) Fiest K.M., Sauro K.M., Wiebe S., Patten S.B., Kwon, C.S., Dykeman, J., Pringsheim, T., Lorenzetti, D.L., Jette N. Prevalence and incidence of epilepsy: A systematic review and meta-analysis of international studies. Neurology, 2017, vol. 88, pp. 296-303. Fiest K.M., Sauro K.M., Wiebe S., Patten S.B., Kwon, C.S., Dykeman, J., Pringsheim, T., Lorenzetti, D.L., Jette N. Prevalence and incidence of epilepsy: A systematic review and meta-analysis of international studies. Neurology, 2017, vol. 88, pp. 296-303. Kramer R.H., Zucker R.S. Calcium-dependent inward current in Aplysia bursting pace-maker neurones. The Journal of Physiology, 1985, vol. 362, no. 1, pp. 107-130. Kramer R.H., Zucker R.S. Calcium-dependent inward current in Aplysia bursting pace-maker neurones. The Journal of Physiology, 1985, vol. 362, no. 1, pp. 107-130. Altrup U., Hader M., Storz U. Endogenous pacemaker potentials develop into paroxysmal. depolarization shifts (PDSs) with application of an epileptogenic drug. Brain Research, 2003, vol. 975, pp. 73-84. Altrup U., Hader M., Storz U. Endogenous pacemaker potentials develop into paroxysmal. depolarization shifts (PDSs) with application of an epileptogenic drug. Brain Research, 2003, vol. 975, pp. 73-84. Kononenko N.I. Dissection of a model for membrane potential oscillations in bursting neuron of snail, Helix pomatia.Comp. Biochem. Physiol, 1994, vol. 107A, pp. 323-332. Kononenko N.I. Dissection of a model for membrane potential oscillations in bursting neuron of snail, Helix pomatia.Comp. Biochem. Physiol, 1994, vol. 107A, pp. 323-332. Garcia Reyes R.C. Study of the dynamics of paroxysmal depolarization shifts in stochastic neuronal models. B.Sc. Thesis, Faculty of Mathematics, Havana University, 2020. Garcia Reyes R.C. Study of the dynamics of paroxysmal depolarization shifts in stochastic neuronal models. B.Sc. Thesis, Faculty of Mathematics, Havana University, 2020. Rezaeva M.N., Khenchel M., Hernandez J.L., Tverdislov V.A. Effect of a number of homologous monoatomic alcohols on the activity of Na, K-ATPase and its reaction with potassium ions. Biofizika, 1980, vol. 25, no. 1, pp. 41-43. Rezaeva M.N., Khenchel M., Hernandez J.L., Tverdislov V.A. Effect of a number of homologous monoatomic alcohols on the activity of Na, K-ATPase and its reaction with potassium ions. Biofizika, 1980, vol. 25, no. 1, pp. 41-43. Hodgkin A.L., Huxley A.F. A quantitative description of membrane current and its application to conduction and excitation in nerve. J. Physiol, 1952, vol. 117, pp. 500-544. Hodgkin A.L., Huxley A.F. A quantitative description of membrane current and its application to conduction and excitation in nerve. J. Physiol, 1952, vol. 117, pp. 500-544. Тасаки И. Нервное возбуждение. Макромолекулярный подход. Москва, Мир, 1971, 224 c. @@Tasaki I. Nervous excitement. Macromolecular approach. Moscow, Mir, 1971, 224 p. (In Russ.) Tasaki I. Nervnoe vozbuzhdenie. Makromolekulyarnyy podhod. Moskva, Mir, 1971, 224 c. @@Tasaki I. Nervous excitement. Macromolecular approach. Moscow, Mir, 1971, 224 p. (In Russ.) Tasaki I., Iwasa K. Rapid pressure changes and surface displacements in the squid giant axon associated with production of action potentials. The Japanese journal of physiology, 1982, vol. 32, no. 1, pp. 69-81. Tasaki I., Iwasa K. Rapid pressure changes and surface displacements in the squid giant axon associated with production of action potentials. The Japanese journal of physiology, 1982, vol. 32, no. 1, pp. 69-81. Артюхов В.Г., Наквасина М.А. Биологические мембраны: структурная организация, функции, модификация физико-химическими агентами: Учеб, пособие. Воронеж: Издательство Воронежского государственного университета, 2000, 296 с. @@Artyukhov V.G., Nakvasina M.A. Biological membranes: structural organization, functions, modification by physico-chemical agents: Textbook, manual. Voronezh: Voronezh State University Publishing House, 2000, 296 p. (In Russ.) Artyuhov V.G., Nakvasina M.A. Biologicheskie membrany: strukturnaya organizaciya, funkcii, modifikaciya fiziko-himicheskimi agentami: Ucheb, posobie. Voronezh: Izdatel'stvo Voronezhskogo gosudarstvennogo universiteta, 2000, 296 s. @@Artyukhov V.G., Nakvasina M.A. Biological membranes: structural organization, functions, modification by physico-chemical agents: Textbook, manual. Voronezh: Voronezh State University Publishing House, 2000, 296 p. (In Russ.) Godfrey J.R., Diaz M.P., Pincus M., Kovacs-Balint Z., Feczko E., Earl E., Miranda-Dominguez O., Fair D., Sanchez M.M., Wilson M.E., Michopoulos V. Diet matters: Glucocorticoid-related neuroadaptations associated with calorie intake in female rhesus monkeys. Psychoneuroendocrinology, 2018, vol. 91, pp. 169-178. Godfrey J.R., Diaz M.P., Pincus M., Kovacs-Balint Z., Feczko E., Earl E., Miranda-Dominguez O., Fair D., Sanchez M.M., Wilson M.E., Michopoulos V. Diet matters: Glucocorticoid-related neuroadaptations associated with calorie intake in female rhesus monkeys. Psychoneuroendocrinology, 2018, vol. 91, pp. 169-178. Abbott B.C., Hill A.V. Howarth J.V. The positive and negative heat production associated with a nerve impulse. Proceedings of the Royal Society of London. Series B-Biological Sciences, 1958, vol. 148, no. 931, pp. 149-187. Abbott B.C., Hill A.V. Howarth J.V. The positive and negative heat production associated with a nerve impulse. Proceedings of the Royal Society of London. Series B-Biological Sciences, 1958, vol. 148, no. 931, pp. 149-187. Keith H.M. Factors influencing experimentally produced convulsions. Arch. Neurol. Psych., 1933, vol. 29, pp. 148-154 Keith H.M. Factors influencing experimentally produced convulsions. Arch. Neurol. Psych., 1933, vol. 29, pp. 148-154 Bough K.J., Rho J.M. Anticonvulsant mechanisms of the ketogenic diet. Epilepsia, 2007, vol. 48, pp. 43-58. Bough K.J., Rho J.M. Anticonvulsant mechanisms of the ketogenic diet. Epilepsia, 2007, vol. 48, pp. 43-58. Keith H.M. The effect of various factors on experimentally produced convulsions. American Journal of Diseases of Children, 1931, vol. 41, no. 3, pp. 532-543. Keith H.M. The effect of various factors on experimentally produced convulsions. American Journal of Diseases of Children, 1931, vol. 41, no. 3, pp. 532-543. Likhodii S.S., Serbanescu I., Cortez M.A., Murphy P., Snead III O.C., Burnham W. M. Anticonvulsant properties of acetone, a brain ketone elevated by the ketogenic diet. Annals of neurology, 2003, vol. 54, no. 2, pp. 219-226. Likhodii S.S., Serbanescu I., Cortez M.A., Murphy P., Snead III O.C., Burnham W. M. Anticonvulsant properties of acetone, a brain ketone elevated by the ketogenic diet. Annals of neurology, 2003, vol. 54, no. 2, pp. 219-226. Seymour K.J., Bluml S., Sutherling J., Sutherling W., Ross B.D. Identification of cerebral acetone by 1H-MRS in patients with epilepsy controlled by ketogenic diet. Magnetic Resonance Materials in Physics, Biology and Medicine, 1999, vol. 8, no. 1, pp. 33-42. Seymour K.J., Bluml S., Sutherling J., Sutherling W., Ross B.D. Identification of cerebral acetone by 1H-MRS in patients with epilepsy controlled by ketogenic diet. Magnetic Resonance Materials in Physics, Biology and Medicine, 1999, vol. 8, no. 1, pp. 33-42. Thio L.L., Wong M., Yamada K.A. Ketone bodies do not directly alter excitatory or inhibitory hippocampal synaptic transmission. Neurology, 2000, vol. 54, no. 2, pp. 325-325. Thio L.L., Wong M., Yamada K.A. Ketone bodies do not directly alter excitatory or inhibitory hippocampal synaptic transmission. Neurology, 2000, vol. 54, no. 2, pp. 325-325. Dyrda G., Boniewska-Bernacka E., Man D., Barchiewicz K., Slota, R. The effect of organic solvents on selected microorganisms and model liposome membrane. Molecular biology reports, 2019, vol. 46, no. 3, pp. 3225-3232. Dyrda G., Boniewska-Bernacka E., Man D., Barchiewicz K., Slota, R. The effect of organic solvents on selected microorganisms and model liposome membrane. Molecular biology reports, 2019, vol. 46, no. 3, pp. 3225-3232. Stovbun S.V., Yakovenko L.V., The Physicochemical Basis of the Biological Activity and Pharmacological Properties of the Antiviral Agent Panavir. Vestnik Moskovskogo Universiteta. Fizika, 2014, no. 6, pp. 101-106. Stovbun S.V., Yakovenko L.V., The Physicochemical Basis of the Biological Activity and Pharmacological Properties of the Antiviral Agent Panavir. Vestnik Moskovskogo Universiteta. Fizika, 2014, no. 6, pp. 101-106. Franks N.P., Lieb W.R. Volatile general anaesthetics activate a novel neuronal K+ current. Nature, 1988, vol. 333, pp. 662-664. Franks N.P., Lieb W.R. Volatile general anaesthetics activate a novel neuronal K+ current. Nature, 1988, vol. 333, pp. 662-664. Junior H.V.N., Fonteles M.M.D.F., Mendes de Freitas R. Acute seizure activity promotes lipid peroxidation, increased nitrite levels and adaptive pathways against oxidative stress in the frontal cortex and striatum. Oxidative medicine and cellular longevity, 2009, vol. 2, no. 3, pp. 130-137. Junior H.V.N., Fonteles M.M.D.F., Mendes de Freitas R. Acute seizure activity promotes lipid peroxidation, increased nitrite levels and adaptive pathways against oxidative stress in the frontal cortex and striatum. Oxidative medicine and cellular longevity, 2009, vol. 2, no. 3, pp. 130-137. Harayama T., Shimizu, T. Roles of polyunsaturated fatty acids, from mediators to membranes. Journal of Lipid Research, 2020, vol. 61, no. 8, pp. 1150-1160. Harayama T., Shimizu, T. Roles of polyunsaturated fatty acids, from mediators to membranes. Journal of Lipid Research, 2020, vol. 61, no. 8, pp. 1150-1160. Martinez-Seara M.H., Rog T., Karttunen M., Vattulainen I., Reigada Kim D.Y., van Brederode H., Sullivan P.G., Spain W.J., Rho J.M., Ketone bodies protect neocortical neurons against acute oxidative stress. Epilepsia, 2004, vol. 45, suppl. 7, p. 199. Martinez-Seara M.H., Rog T., Karttunen M., Vattulainen I., Reigada Kim D.Y., van Brederode H., Sullivan P.G., Spain W.J., Rho J.M., Ketone bodies protect neocortical neurons against acute oxidative stress. Epilepsia, 2004, vol. 45, suppl. 7, p. 199. Нечипуренко Ю.Д., Гарсия Рейес Р.С., Эрнандес Касерес Х.Л. Гипотеза контаминации мембран нейронов при эпилепсии и механизм анти-конвульсивного эффекта кетогенной диеты. Биофизика, в печати. @@Nechipurenko Yu.D., Garcia Reyes R.S., Hernandez Caceres H.L. The hypothesis of contamination of neuronal membranes in epilepsy and the mechanism of the anti-convulsive effect of the ketogenic diet. Biophysics, in press (In Russ.) Nechipurenko Yu.D., Garsiya Reyes R.S., Ernandes Kaseres H.L. Gipoteza kontaminacii membran neyronov pri epilepsii i mehanizm anti-konvul'sivnogo effekta ketogennoy diety. Biofizika, v pechati. @@Nechipurenko Yu.D., Garcia Reyes R.S., Hernandez Caceres H.L. The hypothesis of contamination of neuronal membranes in epilepsy and the mechanism of the anti-convulsive effect of the ketogenic diet. Biophysics, in press (In Russ.)