Long-term serotonin abnormalities in the brain of immature rats subjected to febrile seizures

Document Type : Original Article

Authors

1 Biophysics Department, Faculty of Science, Cairo University, Giza, Egypt

2 Zoology Department, Faculty of Science, Cairo University, Giza, Egypt

Abstract

Objective(s): Febrile seizures (FS) are the most common neurological disorder at a young age in humans. Animal models of hyperthermia-induced seizures provide a tool to investigate the underlying mechanisms of FS related to epilepsy development and its co-morbidities. The present study investigates the alterations in monoamine neurotransmitters in two brain areas: the cortex and the hippo-campus in animals subjected to prolonged FS at their immature age. 
Materials and Methods: Experimental animals were divided into three groups: cage-control group (NHT-NFS), positive hyperthermic control group (HT-NFS), and the hyperthermia-induced febrile seizure group (HT-FS). Each group was further subdivided into young (Y) and adult (A) groups. 
Results: There were significant changes in the cortical and hippocampal serotonin neurotransmitters that were persistent until adulthood. However, the changes in the two other neurotransmitters, norepinephrine and dopamine, were transient and have been recovered in adulthood. 
Conclusion: The present study sheds more light on the importance of monoamine neurotransmitters in epileptogenesis following FS.

Keywords

Main Subjects


1. Reid AY, Galic MA, Teskey GC, Pittman QJ. Febrile seizures: current views and investigations. Can J Neurol Sci. 2009;36:679-686.
2.    Fisher RS, Cross JH, D’souza C, French JA, Haut SR, Higurashi N, et al. Instruction manual for the ILAE 2017 operational classification of seizure types. Epilepsia. 2017;58:531-542.
3.    Patterson JL, Carapetian SA, Hageman JR, Kelley KR. Febrile seizures. Pediatr Ann 2013;42:e258-263.
4.    Acharya UV, Kulanthaivelu K, Panda R, Saini J, Gupta AK, Sankaran BP, et al. Functional network connectivity imprint in febrile seizures. Sci Rep 2022;12:3267-3298.
5.    Leung AK, Hon KL, Leung TN. Febrile seizures: an overview. Drugs Context. 2018;7:212536.
6.    Ben-Ari Y, Holmes GL. Effects of seizures on developmental processes in the immature brain. Lancet Neurol. 2006;5:1055-1063.
7.    Scantlebury MH, Reid AY, Pittman QJ. Contributions of cytokines to febrile seizures. In Febrile Seizures. Academic Press; 2023. p. 179-193.
8.    Pitkänen A, Lukasiuk K, Dudek FE, Staley KJ. Epileptogenesis. Cold Spring Harb Perspect Med. 2015;5:a022822.
9.    Feng B, Chen Z. Generation of febrile seizures and subsequent epileptogenesis. Neurosci Bull 2016;32:481-492.
10.    Kasahara Y, Ikegaya Y, Koyama R. Neonatal seizure models to study epileptogenesis. Front Pharmacol 2018;18:385.
11.    Schuchmann S, Hauck S, Henning S, Grüters‐Kieslich A, Vanhatalo S, Schmitz D, et al. Respiratory alkalosis in children with febrile seizures. Epilepsia 2011;52:1949-1955.
12.    Holtzman D, Obana K, Olson J. Hyperthermia-induced seizures in the rat pup: a model for febrile convulsions in children. Science 1981; 213:1034-1036.
13.    Dube C, Chen K, Eghbal-Ahmadi M, Brunson K, Soltesz I, Baram TZ. Prolonged febrile seizures in the immature rat model enhance hippocampal excitability long term. Ann Neurol 2000;47:336-344.
14.    Jiang W, Duong TM, de Lanerolle NC. The neuropathology of hyperthermic seizures in the rat. Epilepsia 1999;40:5-19.
15.    Avishai-Eliner S, Brunson KL, Sandman CA, Baram TZ. Stressed-out, or in (utero)? Trends Neurosci 2002;25:518-524.
16.    Dubé C, Richichi C, Bender RA, Chung G, Litt B, BaramTZ. Temporal lobe epilepsy after experimental prolonged febrile seizures: prospective analysis. Brain 2006;129:911-922.
17.    Kurian MA, Gissen P, Smith M, Heales SJ, Clayton PT. The monoamine neurotransmitter disorders: An expanding range of neurological syndromes. Lancet Neurol 2011;10:721-733.
18.    Garcia CS. Depression in temporal lobe epilepsy: A review of prevalence, clinical features, and management considerations. Epilepsy Res Treat 2012;2012:809843.
19.    Rocha L, Alonso-Vanegas M, Orozco-Suárez S, Alcántara-González D, Cruzblanca H, Castro E. Do certain signal transduction mechanisms explain the comorbidity of epilepsy and mood disorders? Epilepsy Behav 2014;38:25-31.
20.    Dias R, Bateman LM, Farias ST, Li CS, Lin TC, Jorgensen J, et al. Depression in epilepsy is associated with lack of seizure control. Epilepsy Behav 2010; 19:445-447.
21.    Lacey CJ, Salzberg MR, D’Souza WJ. Risk factors for depression in community-treated epilepsy: Systematic review. Epilepsy Behav 2015;43:1-7.
22.    Kilian M, Frey HH. Central monoamines and convulsive thresholds in mice and rat. Neuropharmacology 1973;12: 681-692.
23.    Bagdy G, Kecskemeti V, Riba P, Jakus R. Serotonin and epilepsy. J Neurochem. 2007; 100:857-873.
24.    Iversen L, Iversen S, Bloom FE, Roth RH. Introduction to neuropsychopharmacology. Oxford Univ Press; 2008.
25.    Bozzi Y, Borrelli E. The role of dopamine signaling in epileptogenesis. Front Cell Neurosci 2013;7:157-168.
26.    Bender RA, Dubé C, Baram TZ. Febrile seizures and mechanisms of epileptogenesis: insights from an animal model. Rec Adv Epilepsy Res. 2004:213-225.
27.    Crespo M, León-Navarro DA, Martin M. Cerebellar oxidative stress and fine motor impairment in adolescent rats exposed to hyperthermia-induced seizures is prevented by maternal caffeine intake during gestation and lactation. Eur J Pharmacol 2018;822:186-198.
28.    Crespo M, León‐Navarro DA, Ruíz MÁ, Martín M. Hyperthermia‐induced seizures produce long‐term effects on the functionality of adenosine A1 receptor in rat cerebral cortex. Int J Dev Neurosci 2020;80:1-2.
29.    Racine RJ. Modification of seizure activity by electrical stimulation: II. Motor seizure. Electroencephalogr Clin Neurophysiol 1972; 32:281-294.
30.    Rijn CM, Krijnen H, Menting-Hermeling S, Coenen AM. Decapitation in rats: latency to unconsciousness and the ‘wave of death’. PLoS One 2011;6:e16514.
31.    Schlumpf M, Lichtensteiger W, Langemann H, Waser PG, Hefti F. A fluorometric micromethod for the simultaneous determination of serotonin, noradrenaline and dopamine in milligram amounts of brain tissue. Biochem Pharmacol 1974;23:2437-2446.
32.    Ciarlone AE, Smudski JW. Lidocaine’s influence on the accumulation and depletion rates of mouse brain amines. J Dent Res 1977;56:1391-1394.
33.    Dubé CM, Brewster AL, Baram TZ. Febrile seizures: Mechanisms and relationship to epilepsy. Brain Dev 2009;31:366-371.
34.    Scantlebury MH, Ouellet PL, Psarropoulou C, Carmant L. Freeze lesion–induced focal cortical dysplasia predisposes to atypical hyperthermic seizures in the immature rat. Epilepsia 2004;45:592-600.
35.    Germano IM, Zhang YF, Sperber EF, Moshé SL. Neuronal migration disorders increase susceptibility to hyperthermia‐induced seizures in developing rats. Epilepsia 1996; 37:902-910.
36.    Rocha L, Lorigados-Pedre L, Orozco-Suárez S, Morales-Chacón L, Alonso-Vanegas M, García-Maeso I, et al. Autoradiography reveals selective changes in serotonin binding in neocortex of patients with temporal lobe epilepsy. Prog Neuropsychopharmacol Biol Psychiatry 2007;31:1208-1218.
37.    Isaac M. Serotonergic 5-HT2C receptors as a potential therapeutic target for the design antiepileptic drugs. Curr Top Med Chem 2005;5:59-67.
38.    Celada P, Puig MV, Artigas F. Serotonin modulation of cortical neurons and networks. Front Integr Neurosci 2013;7:1-20.
39.    Hasler G, Bonwetsch R, Giovacchini G, Toczek MT, Bagic A, Luckenbaugh DA, et al. 5-HT1A receptor binding in temporal lobe epilepsy patients with and without major depression. Biol Psychiatry 2007;62:1258-1264.
40.    da Fonseca NC, Joaquim HP, Talib LL, de Vincentiis S, Gattaz WF, Valente KD. Hippocampal serotonin depletion is related to the presence of generalized tonic–clonic seizures, but not to psychiatric disorders in patients with temporal lobe epilepsy. J Epilepsy Res 2015;111:18-25.
41.    Murugesan A, Rani MS, Hampson J, Zonjy B, Lacuey N, Faingold CL, et al. Serum serotonin levels in patients with epileptic seizures. Epilepsia 2018 ;59:e91-97.
42.    Yuen AW, Thompson PJ, Flugel D, Bell GS, Sander JW. Mortality and morbidity rates are increased in people with epilepsy: Is stress part of the equation? Epilepsy Behav 2007; 10:1-7.
43.    Hiramatsu M, Fujimoto N, Mori A. Catecholamine level in cerebrospinal fluid of epileptics. Neurochem Res 1982;7:1299-1305.
44.    Frosini M, Sesti C, Palmi M, Valoti M, Fusi F, Mantovani P, et al. Heat-stress-induced hyperthermia alters CSF osmolality and composition in conscious rabbits. Am J Physiol Regul Integr Comp Physiol 2000;279:R2095-2103.
45.    Bughdadai FA. Hazardous effects of hyperthermia on brain and testicular responses in rats. Life Sci J 2012;2:9.
46.    Dreier JW, Li J, Sun Y, Christensen J. Evaluation of long-term risk of epilepsy, psychiatric disorders, and mortality among children with recurrent febrile seizures: A national cohort study in Denmark. JAMA Pediatr 2019;173:1164-1170.
47.    Dreier JW, Pedersen CB, Cotsapas C, Christensen J. Childhood seizures and risk of psychiatric disorders in adolescence and early adulthood: A Danish nationwide cohort study. Lancet Child Adolesc health 2019;3:99-108.
48.    Ryan-Coats SK, Hughes SD, Holz FM, Kreger RB, Koulibali CI, Khan HA, et al. Something new and something blue: Responses to novelty in a rodent model of depression and epilepsy comorbidity. Physiol Behav 2022;249:113778.
49.    Bobba PS, Malhotra A, Sheth KN, Taylor SN, Ment LR, Payabvash S. Brain injury patterns in hypoxic ischemic encephalopathy of term neonates. J Neuroimaging 2023;33:79-84.
50.    Herlenius E, Lagercrantz H. Neurotransmitters and neuromodulators during early human development. Early Hum Dev 2001;65:21-37.