Faculty Collaboration Database

Inhibition of protease-activated receptor 1 ameliorates behavioral deficits and restores hippocampal synaptic plasticity in a rat model of status epilepticus. Neurosci Lett 2019 Jan 23;692:64-68

Date

11/06/2018

Pubmed ID

30391321

DOI

10.1016/j.neulet.2018.10.058

Scopus ID

2-s2.0-85056000942 (requires institutional sign-in at Scopus site)   13 Citations

Abstract

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.

Author List

Semenikhina M, Bogovyk R, Fedoriuk M, Nikolaienko O, Al Kury LT, Savotchenko A, Krishtal O, Isaeva E

Author

Olena Isaeva PhD Assistant Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Behavior, Animal
CA1 Region, Hippocampal
Disease Models, Animal
Epilepsy, Temporal Lobe
Lithium
Long-Term Potentiation
Male
Pilocarpine
Pyrroles
Quinazolines
Rats, Wistar
Receptor, PAR-1
Status Epilepticus