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ISSN 2522-9028 (Print)
ISSN 2522-9036 (Online)
DOI: https://doi.org/10.15407/fz

Fiziologichnyi Zhurnal

is a scientific journal issued by the

Bogomoletz Institute of Physiology
National Academy of Sciences of Ukraine

Editor-in-chief: V.F. Sagach

The journal was founded in 1955 as
1955 – 1977 "Fiziolohichnyi zhurnal" (ISSN 0015 – 3311)
1978 – 1993 "Fiziologicheskii zhurnal" (ISSN 0201 – 8489)
1994 – 2016 "Fiziolohichnyi zhurnal" (ISSN 0201 – 8489)
2017 – "Fiziolohichnyi zhurnal" (ISSN 2522-9028)

Fiziol. Zh. 2019; 65(3): 7-11


PHARMACOLOGICAL BLOCKADE OF PROTEASE-ACTIVATED RECEPTORS 1 NORMALIZES BEHAVIORAL HYPEREXCITABILITY OF RATS IN THE LATENT STAGE OF THE EXPERIMENTAL MODEL OF TEMPORAL LOBE EPILEPSY

M. Semenikhina, R. Bogovik, M. Fedoryuk, О. Lunko, A Savotchenko, E. Isaeva

    Bohomoletz Institute of Physiology NAS of Ukraine, Kyiv, Ukraine
DOI: https://doi.org/10.15407/fz65.03.007


Abstract

Temporal lobe epilepsy (TLE) leads to variety of neuropsychological comorbidities, which may have severe impact on social and emotional well-being and significantly reduce the overall quality of life. In the present study, we demonstrate the effect of blocking protease-activated receptor 1 (PAR1), the main thrombin receptor in the central nervous system, on hyperexcitability in the early stages of epilepsy formation. We showed that inhibition of PAR1 leads to the normalization of behavioral hyperexcitability of rats in the latent stage of temporal lobe epilepsy in the lithium-pilocarpine model of status epilepticus (SE) (in the pick-up test which is considered as the most sensitive among tests used in the work: 2.4 ± 0.3 points compared to 3.5 ± 0.58 points for the group after SE). The obtained results correlate with previous studies of the effect of PAR1 inhibition on animal behavior using pharmacological approach and in animals with PAR1 knockout, and provide a further evidence of the role PAR1 in the modulation of affective behavior in TLE.

Keywords: protease-activated receptors 1; lithium-pilocarpine model; status epilepticus; emotional excitability.

References

  1. Trimble M. Treatment issues for personality disorders in epilepsy. Epilepsia. 2013; 54: 41-5. CrossRef PubMed
  2.  
  3. Bogovik R, Lunko O, Fedoriuk M, Isaev D, et al. Effects of protease-activated receptor 1 inhibition on anxiety and fear following status epilepticus. Epilepsy Behav. 2017; 67: 66-9. CrossRef PubMed
  4.  
  5. Isaev D, Lushnikova I, Lunko O, et al. Contribution of protease-activated receptor 1 in status epilepticus-induced epileptogenesis. Neurobiol Dis. 2015; 78: 68-76. CrossRef PubMed PubMedCentral
  6.  
  7. Almonte AG, Qadri LH, Sultan FA, et al. Proteaseactivated receptor-1 modulates hippocampal memory formation and synaptic plasticity. J Neurochem. 2013; 124(1): 109-22. CrossRef PubMed PubMedCentral
  8.  
  9. Maggio N, Cavaliere C, Papa M, et al. Thrombin regulation of synaptic transmission: Implications for seizure onset. Neurobiol Dis. 2013; 171-8. CrossRef PubMed
  10.  
  11. Rice AC, Floyd CL, Lyeth BG, et al. Status Epilepticus Causes Long-Term NMDA Receptor-Dependent Behavioral Changes and Cognitive Deficits. Epilepsia. 1998; 39: 1148-57. CrossRef PubMed
  12.  
  13. Racine RJ. Modification of seizure activity by electrical modification of after-discharge. Electroencephalogr Clin Neurophysiol. 1972; 32: 281-94. CrossRef  
  14. Mikati MA, Holmes GL, Chronopoulos A, et al. Phenobarbital Modifies Seizure-related Brain Injury in the Developing Brain. Ann Neurol. 1994; 36: 425-33. CrossRef PubMed
  15.  
  16. Lunko OO, Bogovyk RI, Fedoriuk MP, et al. The proteaseactivated receptor 1 inhibition during epileptogenesis does not alter behavioral excitability in rats. Fiziol Zh. 2018; 1: 12-8. [Ukrainian] . CrossRef  
  17. Temkin NR, Dikmen SS, Anderson GD, Wilensky AJ, Holmes MD, Cohen W, Newell DW, Nelson P, Awan A WH. Valproate therapy for prevention of posttraumatic seizures: a randomized trial. J Neurosurg. 1999; 91: 593-600. CrossRef PubMed
  18.  
  19. Semenikhina M, Bogovyk R, Fedoriuk M, et al. Inhibition of protease-activated receptor 1 ameliorates behavioral de fi cits and restores hippocampal synaptic plasticity in a rat model of status epilepticus. Neurosci Lett. 2019; 692: 64-8. CrossRef PubMed
  20.  
  21. Semenikhina M, Bogovyk R, Fedoriuk M, et al. Proteaseactivated receptor 1 inhibition does not affect the social behavior after status epilepticus in rat. Fiziol Zh. 2018; 17-22. [Ukrainian]. CrossRef  
  22. Pawlak R, Magarinos AM, Melchor J, et al. Tissue plasminogen activator in the amygdala is critical for stressinduced anxiety-like behavior CA. Nature neurosci. 2003;2:168-74. CrossRef PubMed
  23.  
  24. Horii Y. Increased Anxiety-Like Behavior in Neuropsin (Kallikrein-Related Peptidase 8) Gene-Deficient Mice. Behav Neurosci. 2008; 122: 498-504. CrossRef PubMed
  25.  
  26. Samson AL, Medcalf RL. Tissue-Type Plasminogen Activator : Minireview A Multifaceted Modulator of Neurotransmission and Synaptic Plasticity. Neuron. 2006; 50: 673-8. CrossRef PubMed
  27.  
  28. Maggio N, Itsekson Z, Ikenberg B, et al. The anticoagulant activated protein C (aPC) promotes metaplasticity in the hippocampus through an EPCR-PAR1-S1P1 receptors dependent mechanism. Hippocampus. 2014; 24: 1030-8. CrossRef PubMed
  29.  
  30. Almonte AG, Hamill CE, Chhatwal JP, et al. Learning and memory deficits in mice lacking protease activated receptor-1. Neurobiol Learn Mem. 2007; 88: 295-304. CrossRef PubMed PubMedCentral
  31.  
  32. Bourgognon JM, Schiavon E, Salah-Uddin H, et al. Regulation of neuronal plasticity and fear by a dynamic change in PAR1-G protein coupling in the amygdala. Mol Psychiatry. 2013; 18: 1136-45. CrossRef PubMed PubMedCentral

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