Modulatory effects of delta sleep-inducing peptide in a lindane model of generalized seizures
Keywords:behavior, delta sleep-inducing peptide (DSIP), EEG, epilepsy, refractory seizures lindane
- Efficient drug treatment for resistant forms of epilepsy still haven’t been found. Lindane-induced seizures are refractory to numerous classical antiepileptic drugs. Delta sleep inducing peptide (DSIP) is a neuroprotective nonapeptide capable of optimizing the excitation/inhibition relationship.
- It is not known whether DSIP is capable of modulating refractory seizures. In our work we demonstrated by behavioral and electroencephalographic studies that DSIP can beneficially modulate the severity of lindane-induced seizures and ictal period frequency.
- DSIP has the potential to be an add-on component in antiepileptic treatment strategy for refractory seizures.
Abstract: Delta sleep-inducing peptide (DSIP) is an endogenous peptide that is constantly present in several different brain regions. Lindane is used as a pesticide and scabicide, but it also induces seizures refractory to conventional antiepileptics. The aim of this paper was to determine whether DSIP modulates lindane-induced seizures in rats in a behavioral and electroencephalographic (EEG) study. DSIP (1 mg/kg, i.p.) or dimethyl-sulfoxide (DMSO, 0.5 ml/kg, intraperitoneally (i.p.)) were injected 30 min before lindane (8 mg/kg, i.p.) to adult male rats with previously implanted electrodes for EEG registration. During the following 30 min, the EEG was registered, and the following behavioral characteristics of seizures were observed: incidence, latency and intensity. A descriptive scale with grades from 0 to 4 provided an estimate of seizure intensity. In the EEG, the number and duration of ictal periods were analyzed using NeuroSciLaBG (Belgrade, Serbia) software. The lethality rate was also analyzed. DSIP-treated animals showed significantly modified characteristics of lindane-induced seizures when compared to the group without DSIP pretreatment (i.e. a reduced seizure intensity and a prolonged seizure latency period). However, no significant effects of DSIP on seizure incidence and lindane-induced lethality were observed. EEG analyses showed a significantly decreased number of lindane-induced EEG ictal periods in DSIP-treated animals, but with unaltered duration. These results show that DSIP favorably modulates lindane-induced seizures in rats, showing a potential to be an adjuvant component of antiepileptic treatment strategy for refractory seizures.
Received: January 9, 2018; Revised: February 7, 2018; Accepted: March 30, 2018; Published online: April 19, 2018
How to cite this article: Hrnčić D, Grubač Ž, Šutulović N, Rašić-Marković A, Ademović A, Stanojlović O. Modulatory effects of delta sleep-inducing peptide in a lindane model of generalized seizures. Arch Biol Sci. 2018;70(3):…
Fisher RS, van Emde Boas W, Blume W, Elger C, Genton P, Lee P, Engel J Jr. Epileptic seizures and epilepsy: definitions proposed by the International League Against Epilepsy (ILAE) and the International Bureau for Epilepsy (IBE). Epilepsia. 2005;46(4):470-2.
Chang BS, Lowenstein DH. Epilepsy. N Engl J Med 2003;349(13):1257-66.
Ngugi AK, Kariuki SM, Bottomley C, Kleinschmidt I, Sander JW, Newton CR. Incidence of epilepsy: systematic review and meta-analysis. Neurology. 2011;77(10):1005-12.
Pugliatti M, Beghi E, Forsgren L, Ekman M, Sobocki P. Estimating the cost of epilepsy in Europe: a review with economic modeling. Epilepsia. 2007;48(12):2224-33.
Beghi E, Berg A, Carpio A, Forsgren L, Hesdorffer DC, Hauser WA, Malmgren K, Shinnar S, Temkin N, Thurman D, Tomson T. Coment on epileptic seizures and epilepsy: definitions proposed by the International League Against Epilepsy (ILAE) and the International Bureau for Epilepsy (IBE). Epilepsia. 2005;46(10):1698-9.
Strine TW, Chapman DP. Associations of frequent sleep insufficiency with health-related quality of life and health behaviors. Sleep Med. 2005;6(1):23-7.
Hindmarch I , Dawson J, Stanley N. A double-blind study in healthy volunteers to assess the effects on sleep of pregabalin compared with alprazolam and placebo. Sleep. 2005;28(2):187-93.
Drake ME Jr, Pakalnis A, Bogner JE, Andrews JM. Outpatient sleep recording during antiepileptic drug monotherapy. Clin Electroencephal. 1990;21(3):170-3.
Legros B, Bazil CW. Effects of antiepileptic drugs on sleep architecture: a pilot study. Sleep Med 2003;4(1):51-5.
Placidi F, Diomedi M, Scalise A, Marciani MG, Romigi A, Gigli GL. Effect of anticonvulsants on nocturnal sleep in epilepsy. Neurology. 2000;54(5):25-32.
Sinha SR. Basic mechanisms of sleep and epilepsy. J Clin Neurophysiol 2011;28(2):103-10.
Jiruska P, de Curtis M, Jefferys JG, Schevon CA, Schiff SJ, Schindler K. Synchronization and desynchronization in epilepsy: controversies and hypotheses. J Physiol. 2013;591(4):787-97.
Niethard N, Burgalossi A, Born J. Plasticity during sleep is linked to specific regulation of cortical circuit activity. Front Neural Circuits. 2017;11:65.
Halász P. How sleep activates epileptic networks? Epilepsy Res Treat. 2013;2013:425-697.
Coenen AM, Van Luijtelaar EL. Genetic animal models for absence epilepsy: a review of the WAG/Rij strain of rats. Behav Genet. 2003;33(6):635-55.
Monnier M, Dudler L, Gächter R, Schoenenberger GA. Delta-sleep-inducing peptide (DSIP): EEG and motor activity in rabbits following intravenous administration. Neurosci Lett. 1977;6(1):9-13.
Sudakova KV, Umriukhina PE, Rayevskyb KS. Delta-sleep inducing peptide and neuronal activity after glutamate microiontophoresis: the role of NMDA-receptors. Pathophysiol. 2004;11(2):81-6.
Shandra AA, Godlevskii LS , Brusentsov AI, Karlyuga VA. Effects of delta-sleep-inducing peptide on NMDA-induced convulsive activity in rats. Neurosci Behav Physiol. 1998;28(6):694-7.
Sudakov KV, Coghlan JP, Kotov AV, Salieva RM, Polyntsev YuV, Koplik EV. Delta-sleep inducing peptide sequels in mechanisms of resistance to emotional stress. Ann N Y Acad Sci. 1995;771:240-51.
Khvatova EM, Samartzev VN, Zagoskin PP, Prudchenko IA, Mikhaleva II. Delta sleep inducing peptide (DSIP): effect on respiration activity in rat brain mitochondria and stress protective potency under experimental hypoxia. Peptides. 2003;24(2):307-11.
Yehuda S, Carasso RL. DSIP--a tool for investigating the sleep onset mechanism: a review. Int J Neurosci 1988;38(3-4):345-53.
Secretariat of the Stockholm Convention. Report of the Conference of the Parties of the Stockholm Convention on Persistent Organic Pollutants on the work of its fourth meeting. Geneva (Switzerland): Secretariat of the Stockholm Convention on Persistent Organic Pollutants; 2009 May. 24 p. Report No.:UNEP/POPS/COP.4/6/Rev.1
Li Y. Global technical hexachlorocyclohexane usage and contamination consequences in the environment: from 1948 to 1997. Sci Total Environ. 1999;121-58.
Centers for Disease Control and Prevention (CDC). Unintentional topical lindane ingestions-United States. 1998-2003. MMWR Morb Mortal Wkly Rep. 2005;54(21):533-5.
Vucević D, Hrncić D, Radosavljević T, Mladenović D, Rasić-Marković A, Loncar-Stevanović H, Djurić D, Macut D, Susić V, Stanojlović O. Corellation between electrocorticographic and motor phenomena in lindane induced experimental epilepsy in rats. Can J Physiol Pharmacol. 2008;86(4):173-9.
Nolan K, Kamrath J, Levitt J. Lindane toxicity: a comprehensive review of the medical literature. Pediatr Dermatol. 2012 ;29(2):141-6.
Czuszwar SJ, Borowicz KK. Polytherapy in epilepsy: the experimental evidence. Epilepsy Res 2002;52(1):15-23.
Tochman AM , Kaminski R , Turski WA , Czuczwar SJ. Protection by conventional and new antiepileptic drugs against lindane-induced seizures and lethal effects in mice. Neurotox Res. 2000;2(1):63-70.
Hrnčić D, Rašić-Marković A, Djuric D, Stanojlović O. The role of nitric oxide in convulsions induced by lindane in rats. Food Chem Toxicol. 2011;49(4):947-54.
Stanojlović OP, Živanović DP, Mirković SD, Mikhaleva II. Antiepileptic activity of delta sleep inducing peptide and its analogue in metaphit-provoked seizures in rats. Seizures. 2005;14:240-7.
Kovalzon VM, Strekalova TV. Delta sleep-inducing peptide (DSIP): a still unresolved riddle. J Neurochem. 2006;97(2):303-9.
Engelborghs S, D'Hooge R, De Deyn PP. Pathophysiology of epilepsy. Acta Neurol Belg. 2000;100(4):201-13.
Suñol C, Tusell JM, Gelpí E, Rodríguez-Farré E. Convulsant effect of lindane and regional brain concentration of GABA and dopamine. Toxicology. 1988;49(2-3):247-52.
Anand M., Agrawa AK, Rehmani BNH. Role of GABA receptor complex in low dose lindane (HCH) induced neurotoxicity: neurobehavioural, neurochemical and electrophysiological studies. Drug Chem Toxicol. 1998;21(1):35-46.
Suñol C, Vale C, Rodríguez-Farré E. Polychlorocycloalkane insecticide action on GABA- and glycine-dependent chlorine flux. Neurotoxicology. 1998;19(4-5):573-80.
Rosa R, Sanfeliu C, Suñol C, Pomés A, Rodríguez-Farré E, Schousboe A, Frandsen A. The mechanism for hexachlorocyclohexane-induced cytotoxicity and changes in intracellular Ca²+ homeostasis in cultured cerebellar granule neurons is different from the gamma- and delta-isomers. Toxicol Appl Pharmacol. 1997;142(1):31-9.
Grigor'ev VV, Ivanova TA, Kustova EA, Petrova LN, Serkova TP, Bachurin SO. Effects of delta sleep-inducing peptide on pre- and postsynaptic glutamate and postsynaptic GABA receptors in neurons of the cortex, hippocampus, and cerebellum in rats. Bull Exp Biol Med. 2006;142(2):186-8.
Mendzheritski AM, Lysenko AV, Uskova NI, Sametkii EA. Studies of the mechanism of the anticonvulsant effect of delta-sleep-inducing peptide in conditions of increased oxygen tension. Neurosci Behav Physiol. 1997;27(6):714-7.
Sudha K, Rao AV, Rao A. Oxidative stress and antioxidants in epilepsy. Clin Chim Acta. 2001;303(1-2):19-24.
Puttachary S, Sharma S, Stark S, Thippeswamy T. Seizure-induced oxidative stress in temporal lobe epilepsy. Biomed Res Int. 2015;2015:745613.
Shustanova TA, Bondarenko TI, Milyutina NP, Mikhaleva II. Regulation of free radical processes by delta-sleep inducing peptide in rat tissues under cold stress. Biochemistry (Mosc). 2001;66(6):632-9.
Bobyntsev II, Kryukov AA, Belykh AE, Dudka VT. Effect of Delta Sleep-Inducing Peptide on Functional State of Hepatocytes in Rats During Restraint Stress. Bull Exp Biol Med. 2016;160(4):421-4.
Kutilin DS, Bondarenko TI, Kornienko IV, Mikhaleva II. Effect of delta sleep-inducing peptide on the expression of antioxidant enzyme genes in the brain and blood of rats during physiological aging. Bull Exp Biol Med. 2014;157(5):616-9.
Bondarenko TI, Miliutina NP, Mikhaleva II, Noskova NV. Membrane-stabilizing effect of delta sleep-inducing peptide during stress. Bull Exp Biol Med. 1998;126(9):325-7.
Polverini E, Casadio R, Neyroz P, Masotti L. Conformational changes of neuromedin B and delta sleep-inducing peptide induced by their interaction with lipid membranes as revealed by spectroscopic techniques and molecular dynamics simulation. Arch Biochem Biophys. 1998;349(2):225-35.
Mendzeritsky A, Matsionis A, Lysenko A. The protective effect of delta sleep - inducing peptide under hypokinetic stress. In: Teelken A, Korf J. Neurochemistry. New York: Springer US; 1997. p. 393-43.
Umbriukhin PE. Delta sleep-inducing peptide blocks excitatory effect of glutamate on rat brain neurons. Bull Exp Biol Med. 2002;134(1):5-7.
Prudchenko IA, Stashevskaia LV, Mikhaleva II, Ivanov VT, Shandra AA, Godlevskiĭ LS, Mazarati AM. Synthesis and biological properties of a series of new analogues of delta-sleep peptide. Bioorg Khim. 1993;19(1):43-55.
Lothman EW, Collins RC, Ferrendelli JA. Kainic acid-induced limbic seizures: electrophysiologic studies. Neurology. 1881;31(7):806-12.
Borowicz KK, Czuczwar SJ. Effects of etomidate, ketamine or propofol and their combinations with conventional antiepileptic drugs on amygdala-kindled convulsions in rats. Neuropharmacology. 2003;45(3):315-24.
Pan W, Kastin AJ. The blood-brain barrier: regulatory roles in wakefulness and sleep. Neuroscientist. 2016;pii:1073858416639005.
Augustijns PF, Borchardt RT. Transport and metabolism of delta sleep-inducing peptide in cultured human intestinal epithelial cell monolayers. Drug Metab Dispos. 1995; 23(12):1372-8.
Koplik EV, Umryukhin PE, Konorova IL, Terekhina OL, Mikhaleva II, Gannushkina IV, Sudakov KV. Delta sleep-inducing peptide and Deltaran: potential approaches to antistress protection. Neurosci Behav Physiol. 2008;38(9):953-7.
Popovich IG, Voitenkov BO, Anisimov VN, Ivanov VT, Mikhaleva II, Zabezhinski MA, Alimova IN, Baturin DA, Zavarzina NY, Rosenfeld SV, Semenchenko AV, Yashin AI. Effect of delta-sleep inducing peptide-containing preparation Deltaran on biomarkers of aging, life span and spontaneous tumor incidence in female SHR mice. Mech Ageing Dev. 2003;124(6):721-31.
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