Anticonvulsant Activity of Pterostilbene in Zebrafish and Mouse Acute Seizure Tests

Abstract

Pterostilbene (PTE), a natural dimethylated analog of resveratrol, possesses numerous health-beneficial properties. The ability of PTE to cross the blood–brain barrier raised the possibility that this compound may modulate central nervous system functions, including seizure activity. The aim of our study was to investigate the activity of PTE in the larval zebrafish pentylenetetrazole (PTZ) seizure assay and three acute seizure tests in mice, i.e., in the maximal electroshock seizure threshold (MEST), 6 Hz-induced psychomotor seizure threshold and intravenous ( iv ) PTZ tests. Additionally, potential antidepressant activity of PTE was estimated in the forced swim test in mice. The chimney test was used to determine the influence of PTE on motor coordination in mice, while its influence on neuromuscular strength was assessed in the grip strength test in mice. Locomotor activity was determined to verify the results from the forced swim test. PTE revealed an evident anticonvulsant effect both in zebrafish larvae (10 µM; 2 h-incubation) and mice (at doses of 100 and 200 mg/kg, intraperitoneally) but it did not exhibit antidepressant potential in the forced swim test. Furthermore, it did not cause any statistically significant changes in motor coordination, neuromuscular strength and locomotor activity in mice. In conclusion, our present findings demonstrate for the first time the anticonvulsant potential of PTE. The aforementioned results suggest that it might be employed in epilepsy treatment, however, further precise studies are required to verify its activity in other experimental seizure and epilepsy models and its precise mechanism of action should be determined.

Phenotypic Characterization of Larval Zebrafish (Danio rerio) with Partial Knockdown of the cacna1a Gene

“…In order to detect epileptiform-like discharges in zebrafish larvae, the EEG recordings were conducted according to the method described previously [39].…”

N-Benzyl-(2,5-dioxopyrrolidin-1-yl)propanamide (AS-1) with Hybrid Structure as a Candidate for a Broad-Spectrum Antiepileptic Drug

“…We found out that the preincubation of larval zebrafish with AS-1 decreased the number and cumulative duration of EEG discharges induced by acute PTZ. This proconvulsant in larval zebrafish induces a number of behavioral changes, starting with burst swimming and culminating in tonic-clonic convulsions, resembling epileptic seizures in mammals [34,63,64]. At the EEG level, exposure to PTZ induces frequent, recurrent ictal-like discharges [33,65].…”

“…At the EEG level, exposure to PTZ induces frequent, recurrent ictal-like discharges [33,65]. To date, the zebrafish PTZ assay has been validated and extensively characterized using commercially available AEDs [33,66], while obtained results have been proved to translate well to rodent models [34,65,67,68].…”

“…After incubation, larvae were exposed to vehicle or 20 mM PTZ for 5 min. Next, larvae were immobilized in a thin layer of 2% low-melting-point agarose and the glass electrode (resistance 1-5 MΩ) filled with artificial cerebrospinal fluid (124 mM NaCl, 2 mM KCl, 2 mM MgSO 4 , 2 mM CaCl 2 , 1.25 mM KH 2 PO 4 , 26 mM NaHCO 3 , 10 mM glucose) was placed into the optic tectum (MultiClamp 700B amplifier, Digidata 1440A digitizer; Molecular Devices, San Jose, CA) [33,34]. Single recordings for each larva were performed for a period of 20 min.…”

Characterization of Effectiveness in Concerted Ih Inhibition and IK(Ca) Stimulation by Pterostilbene (Trans-3,5-dimethoxy-4′-hydroxystilbene), a Stilbenoid

“…Recent evidence has revealed that PTER could exert protective actions against the oxidative stress or inflammatory reaction in various types of neurons, such as neuronal SH-SY5Y cells and spinal cord neurons, as well as in ischemia-or hypoxia-induced brain injuries [14][15][16][17][18][19][20][21]. PTER and other resveratrol analogs were previously reported to exert antiepileptic actions [22][23][24] to decrease dopamine release in striatal slices, and to substantially ameliorate depressive or cognitive behavioral deficits in rats [25][26][27]. It is also noted that the presence of PTER could disrupt pituitary function [3,28].…”