Inhibition of protease-activated receptor 1 ameliorates behavioral deficits and restores hippocampal synaptic plasticity in a rat model of status epilepticus

Author First name, Last name, Institution

Marharyta Semenikhina, Bogomoletz Institute of Physiology
Ruslan Bogovyk, Bogomoletz Institute of Physiology
Mykhailo Fedoriuk, Bogomoletz Institute of Physiology
Oksana Nikolaienko, Bogomoletz Institute of Physiology
Lina T. AlKury, Zayed UniversityFollow
Alina Savotchenko, Bogomoletz Institute of Physiology
Oleg Krishtal, Bogomoletz Institute of Physiology
Elena Isaeva, Bogomoletz Institute of Physiology

ORCID Identifiers

0000-0002-3999-4570

0000-0002-0587-6322

Document Type

Article

Source of Publication

Neuroscience Letters

Publication Date

1-23-2019

Abstract

© 2018 The blood-brain barrier (BBB) is a unique structure that controls substances exchange between the systemic circulation and the brain. Disruption of its integrity contributes to the development and progression of a variety of brain disorders including stroke, epilepsy and neurodegenerative diseases. It was shown that intracerebral thrombin level substantially increases following status epilepticus (SE). Inhibition of protease-activated receptor 1 (PAR1), the major thrombin receptor in the brain, produces an anti-epileptogenic and neuroprotective effects in an experimental model of temporal lobe epilepsy (TLE). Since serine proteases and PAR1 are implicated in the synaptic plasticity and memory formation, the aim of the present study was to elucidate the involvement of PAR1 in synaptic plasticity and behavior deficits following SE. Using lithium-pilocarpine model of TLE, we demonstrate that inhibition of PAR1 rescues SE-induced synaptic plasticity deficits in CA1 region of hippocampus. Although treatment with PAR1 antagonist does not ameliorate spatial learning deficits, it attenuates anxiolytic-like behavior in experimental rats after SE. Taken together; our data suggest an important role of PAR1 in SE-induced synaptic and behavioral alterations and provide a new insight into cellular mechanisms underlying behavioral impairments associated with epilepsy.

DOI Link

10.1016/j.neulet.2018.10.058

ISSN

0304-3940

Publisher

Elsevier Ireland Ltd

Volume

692

First Page

64

Last Page

68

Disciplines

Chemistry | Education | Life Sciences | Medicine and Health Sciences

Keywords

Anxiety, Lithium-pilocarpine model, Protease-activated receptor 1, Spatial memory, Synaptic plasticity, Temporal lobe epilepsy

Scopus ID

85056000942

Recommended Citation

Semenikhina, Marharyta; Bogovyk, Ruslan; Fedoriuk, Mykhailo; Nikolaienko, Oksana; AlKury, Lina T.; Savotchenko, Alina; Krishtal, Oleg; and Isaeva, Elena, "Inhibition of protease-activated receptor 1 ameliorates behavioral deficits and restores hippocampal synaptic plasticity in a rat model of status epilepticus" (2019). All Works. 2017.
https://zuscholars.zu.ac.ae/works/2017

Indexed in Scopus

yes

Open Access

no