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