PDF herunterladen
CC BY-NC-ND 4.0 · International Journal of Epilepsy 2017; 04(01): 036-045
DOI: 10.1016/j.ijep.2016.12.005
Research paper
Thieme Medical and Scientific Publishers Private Ltd.

Early-life status epilepticus induces long-term deficits in anxiety and spatial learning in mice

Gregory Smith
a   Institute of Biomedical Sciences, Baylor University, Waco, TX 76798, USA
,
Nowrin Ahmed
b   Department of Psychology and Neuroscience, Baylor University, Waco, TX 76798, USA
,
Erin Arbuckle
a   Institute of Biomedical Sciences, Baylor University, Waco, TX 76798, USA
,
Joaquin N. Lugo
a   Institute of Biomedical Sciences, Baylor University, Waco, TX 76798, USA
b   Department of Psychology and Neuroscience, Baylor University, Waco, TX 76798, USA
› Institutsangaben
Weitere Informationen

Publikationsverlauf

Received: 01. August 2016

Accepted: 19. Dezember 2016

Publikationsdatum:
06. Mai 2018 (online)

Auch verfügbar auf
   Lizenzen und Reprints

Abstract

Background One of the most devastating aspects of developmental epilepsy is the long-term impact on behavior. Children with epilepsy show a high co-morbidity with anxiety disorders and autism.

Methods To examine whether early-life status epilepticus results in altered anxiety, repetitive behavior, social behavior, and learning and memory, we induced status epilepticus in male C57BL/6 mice on postnatal day (PD) 10. The mice received intraperitoneal injections of either kainic acid (2 mg/kg) or 0.9% normal saline. We also included a nontreated control group. Kainic acid induced status epilepticus for approximately 1.5 h. At PD60, the adult mice were then tested in a battery of behavioral tasks, including open field activity, elevated-plus maze, light-dark test, marble burying, social chamber, social partition, conditioned fear, novel object recognition, and Morris water maze.

Results The early-life seizure group showed consistent increases in anxiety in the open field test (p < 0.05), elevated plus maze (p < 0.05), and light-dark task (p < 0.01). The seizure group showed significant (p < 0.01) impairment in the Morris water maze. There were no differences observed in marble burying, social partition, social chamber, novel object recognition, or delay fear conditioning tasks.

Conclusions These results demonstrate that a single insult of status epilepticus during the neonatal period is sufficient to cause specific, long-term impairments in anxiety and spatial learning.

Keywords

Anxiety - Behavior - Social behavior - Learning and memory - Early development
 

  • References

  • 1 Camfield CS, Camfield PR, Gordon K, Wirrell E, Dooley JM. Incidence of epilepsy in childhood and adolescence: a population-based study in Nova Scotia from 1977 to 1985. Epilepsia 37 1996; 19-23
    CrossrefPubMedGoogle Scholar
  • 2 Holmes GL, Ben-Ari Y. The neurobiology and consequences of epilepsy in the developing brain. Pediatr Res 49 2001; 320-325
    CrossrefPubMedGoogle Scholar
  • 3 Koh S, Storey TW, Santos TC, Mian AY, Cole AJ. Early-life seizures in rats increase susceptibility to seizure-induced brain injury in adulthood. Neurology 53 1999; 915-921
    CrossrefPubMedGoogle Scholar
  • 4 Gross-Tsur V, Shinnar S. Convulsive status epilepticus in children. Epilepsia 34 Suppl. (01) 1993; S12-20
    CrossrefPubMedGoogle Scholar
  • 5 Aicardi J, Chevrie JJ. Convulsive status epilepticus in infants and children. A study of 239 cases. Epilepsia 11 1970; 187-197
    CrossrefPubMedGoogle Scholar
  • 6 Matsumoto A, Watanabe K, Sugiura M, Negoro T, Takaesu E, Iwase K. Long-term prognosis of convulsive disorders in the first year of life: mental and physical development and seizure persistence. Epilepsia 24 1983; 321-329
    CrossrefPubMedGoogle Scholar
  • 7 Baxendale S, Heaney D, Thompson PJ, Duncan JS. Cognitive consequences of childhood-onset temporal lobe epilepsy across the adult lifespan. Neurology 75 2010; 705-711
    CrossrefPubMedGoogle Scholar
  • 8 Berg AT. Epilepsy, cognition, and behavior: the clinical picture. Epilepsia 52 Suppl. (01) 2011; 7-12
    PubMedGoogle Scholar
  • 9 Nolan MA, Redoblado MA, Lah S. et al. Intelligence in childhood epilepsy syndromes. Epilepsy Res 53 2003; 139-150
    CrossrefPubMedGoogle Scholar
  • 10 Beyenburg S, Mitchell AJ, Schmidt D, Elger CE, Reuber M. Anxiety in patients with epilepsy: systematic review and suggestions for clinical management. Epilepsy Behav 7 2005; 161-171
    CrossrefPubMedGoogle Scholar
  • 11 Reilly C, Agnew R, Neville BG. Depression and anxiety in childhood epilepsy: a review. Seizure 20 2011; 589-597
    CrossrefPubMedGoogle Scholar
  • 12 Clarke DF, Roberts W, Daraksan M. et al. The prevalence of autistic spectrum disorder in children surveyed in a tertiary care epilepsy clinic. Epilepsia 46 2005; 1970-1977
    CrossrefPubMedGoogle Scholar
  • 13 Meidenbauer JJ, Mantis JG, Seyfried TN. The EL mouse: a natural model of autism and epilepsy. Epilepsia. 2011
    PubMedGoogle Scholar
  • 14 Niemeyer MI, Cid LP, Sepúlveda FV, Blanz J, Auberson M, Jentsch TJ. No evidence for a role of CLCN2 variants in idiopathic generalized epilepsy. Nat Genet 12 2010; 3
    PubMedGoogle Scholar
  • 15 Bernard PB, Castano AM, O'Leary H, Simpson K, Browning MD, Benke TA. Phosphorylation of FMRP and alterations of FMRP complex underlie enhanced mLTD in adult rats triggered by early life seizures. Neurobiol Dis. 2013
    PubMedGoogle Scholar
  • 16 Cornejo BJ, Mesches MH, Coultrap S, Browning MD, Benke TA. A single episode of neonatal seizures permanently alters glutamatergic synapses. Ann Neurol 61 2007; 411-426
    CrossrefPubMedGoogle Scholar
  • 17 Castelhano AS, Cassane Gdos S, Scorza FA, Cysneiros RM. Altered anxiety-related and abnormal social behaviors in rats exposed to early life seizures. Front Behav Neurosci 7 2013; 36
    PubMedGoogle Scholar
  • 18 Holmes GL, Gairsa JL, Chevassus-Au-Louis N, Ben-Ari Y. Consequences of neonatal seizures in the rat: morphological and behavioral effects. Ann Neurol 44 1998; 845-857
    CrossrefPubMedGoogle Scholar
  • 19 Moreira JD, de Siqueira LV, Lague VM, Porciuncula LO, Vinade L, Souza DO. Short-term alterations in hippocampal glutamate transport system caused by one-single neonatal seizure episode: implications on behavioral performance in adulthood. Neurochem Int 59 2011; 217-223
    CrossrefPubMedGoogle Scholar
  • 20 Muller CJ, Bankstahl M, Groticke I, Loscher W. Pilocarpine vs lithium-pilocarpine for induction of status epilepticus in mice: development of spontaneous seizures, behavioral alterations and neuronal damage. Eur J Pharmacol 619 2009; 15-24
    CrossrefPubMedGoogle Scholar
  • 21 Muller CJ, Groticke I, Bankstahl M, Loscher W. Behavioral and cognitive alterations, spontaneous seizures, and neuropathology developing after a pilocarpine-induced status epilepticus in C57BL/6 mice. Exp Neurol 219 2009; 284-297
    CrossrefPubMedGoogle Scholar
  • 22 Sayin U, Sutula TP, Stafstrom CE. Seizures in the developing brain cause adverse long-term effects on spatial learning and anxiety. Epilepsia 45 2004; 1539-1548
    CrossrefPubMedGoogle Scholar
  • 23 Cornejo BJ, Mesches MH, Benke TA. A single early-life seizure impairs short-term memory but does not alter spatial learning, recognition memory, or anxiety. Epilepsy Behav 13 2008; 585-592
    CrossrefPubMedGoogle Scholar
  • 24 Lugo JN, Swann JW, Anderson AE. Early-life seizures result in deficits in social behavior and learning. Exp Neurol. 2014
    PubMedGoogle Scholar
  • 25 Bernard PB, Castano AM, Beitzel CS, Carlson VB, Benke TA. Behavioral changes following a single episode of early-life seizures support the latent development of an autistic phenotype. Epilepsy Behav 44 2015; 78-85
    CrossrefPubMedGoogle Scholar
  • 26 Barnwell LF, Lugo JN, Lee WL. et al. Kv4.2 knockout mice demonstrate increased susceptibility to convulsant stimulation. Epilepsia 50 2009; 1741-1751
    CrossrefPubMedGoogle Scholar
  • 27 Pellow S, Chopin P, File SE, Briley M. Validation of open:closed arm entries in an elevated plus-maze as a measure of anxiety in the rat. J Neurosci Methods 14 1985; 149-167
    CrossrefPubMedGoogle Scholar
  • 28 Shimada T, Matsumoto K, Osanai M, Matsuda H, Terasawa K, Watanabe H. The modified light/dark transition test in mice: evaluation of classic and putative anxiolytic and anxiogenic drugs. Gen Pharmacol 26 1995; 205-210
    CrossrefPubMedGoogle Scholar
  • 29 Spencer CM, Alekseyenko O, Serysheva E, Yuva-Paylor LA, Paylor R. Altered anxiety-related and social behaviors in the Fmr1 knockout mouse model of fragile X syndrome. Genes Brain Behav 4 2005; 420-430
    CrossrefPubMedGoogle Scholar
  • 30 McIlwain KL, Merriweather MY, Yuva-Paylor LA, Paylor R. The use of behavioral test batteries: effects of training history. Physiol Behav 73 2001; 705-717
    CrossrefPubMedGoogle Scholar
  • 31 Bevins RA, Besheer J. Object recognition in rats and mice: a one-trial non-matching-to-sample learning task to study ‘recognition memory'. Nat Protoc 1 2006; 1306-1311
    CrossrefPubMedGoogle Scholar
  • 32 Swinkels WA, Kuyk J, de Graaf EH, van Dyck R, Spinhoven P. Prevalence of psychopathology in dutch epilepsy inpatients: a comparative study. Epilepsy Behav 2 2001; 441-447
    CrossrefPubMedGoogle Scholar
  • 33 Ettinger AB, Weisbrot DM, Nolan EE. et al. Symptoms of depression and anxiety in pediatric epilepsy patients. Epilepsia 39 1998; 595-599
    CrossrefPubMedGoogle Scholar
  • 34 Jones JE, Hermann BP, Barry JJ, Gilliam F, Kanner AM, Meador KJ. Clinical assessment of axis I psychiatric morbidity in chronic epilepsy: a multicenter investigation. J Neuropsychiatry Clin Neurosci 17 2005; 172-179
    CrossrefPubMedGoogle Scholar
  • 35 Wahlsten D. Mouse behavioral testing: how to use mice in behavioral neuroscience. Mouse Behavioral Testing: How to Use Mice in Behavioral Neuroscience. 2011: 1-288
    PubMedGoogle Scholar
  • 36 Boleij H, Salomons AR, van Sprundel M, Arndt SS, Ohl F. Not all mice are equal: welfare implications of behavioural habituation profiles in four 129 mouse substrains. PLoS One. 7. 2012
    PubMedGoogle Scholar
  • 37 Stafstrom CE. Assessing the behavioral and cognitive effects of seizures on the developing brain. Prog Brain Res 135 2002; 377-390
    PubMedGoogle Scholar
  • 38 Holmes GL, Tian C, Hernan AE, Flynn S, Camp D, Barry J. Alterations in sociability and functional brain connectivity caused by early-life seizures are prevented by bumetanide. Neurobiol Dis 77 2015; 204-219
    CrossrefPubMedGoogle Scholar
  • 39 Canitano R. Epilepsy in autism spectrum disorders. Eur Child Adolesc Psychiatry 16 2007; 61-66
    CrossrefPubMedGoogle Scholar
  • 40 Tuchman R, Moshe SL, Rapin I. Convulsing toward the pathophysiology of autism. Brain Dev 31 2009; 95-103
    CrossrefPubMedGoogle Scholar
  • 41 Karnam HB, Zhou JL, Huang LT, Zhao Q, Shatskikh T, Holmes GL. Early life seizures cause long-standing impairment of the hippocampal map. Exp Neurol 217 2009; 378-387
    CrossrefPubMedGoogle Scholar
  • 42 Boyce R, Leung LS. Loss of dendritic inhibition in the hippocampus after repeated early-life hyperthermic seizures in rats. Epilepsy Res 103 2013; 62-72
    CrossrefPubMedGoogle Scholar
  • 43 Nishimura M, Gu X, Swann JW. Seizures in early life suppress hippocampal dendrite growth while impairing spatial learning. Neurobiol Dis 44 2011; 205-214
    CrossrefPubMedGoogle Scholar
  • 44 Mumby DG. Perspectives on object-recognition memory following hippocampal damage: lessons from studies in rats. Behav Brain Res 127 2001; 159-181
    CrossrefPubMedGoogle Scholar
  • 45 Ekinci O, Titus JB, Rodopman AA, Berkem M, Trevathan E. Depression and anxiety in children and adolescents with epilepsy: prevalence, risk factors, and treatment. Epilepsy Behav 14 2009; 8-18
    CrossrefPubMedGoogle Scholar