Marta Marszałek-Grabska, Monika Hułas-Stasiak, Saadat Bekenova, Anna Grenda, Michał Szulc, Camila V Esguerra, Sohee Kim, Waldemar A Turski, Kinga Gaweł
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引用次数: 0
Abstract
Background: Recently, it has been reported that pilocarpine (PILO) induces seizures in zebrafish larvae. It has also been shown that acute PILO-induced convulsions result in unprovoked seizure-like discharges 24 hours later. Since lithium (Li) pretreatment potentiates the convulsions induced by PILO in rodents, this study was undertaken to evaluate the effect of Li on PILO-induced seizures in zebrafish larvae.
Methods: Experiments were conducted on zebrafish larvae up to 5 days post-fertilization. Larvae were pre-exposed to Li and then exposed to PILO. Local field potentials from the optic tectum were recorded and subjected to quantitative spectral analysis, including power spectral density estimation, band-specific power analysis, and automated ictal-event detection based on root mean square thresholding. Locomotor activity, followed by quartile-based population analysis as a potential behavioral correlate of seizure activity, was investigated. TUNEL-based apoptosis quantification and mRNA expression of neuronal activity markers npas4α and c-fos were examined.
Results: It was found, that pre-exposure to Li does not affect PILO-induced seizures. PILO induced seizure-like discharges in Li-pretreated larvae comparable to those evoked by PILO alone, and similarly to PILO, resulted in spontaneous, unprovoked paroxysmal brain activity 24 hours post-exposure. Spectral analysis revealed persistent increases in theta, alpha, and beta band power at the 24-hour time point, accompanied by brain apoptosis. At this time, an increase in npas4α expression was found in naïve larvae exposed to PILO. Results of quartile-based locomotor analysis, but not aggregate distance measures, correlate with seizure-like activity.
Conclusions: Both PILO and Li+PILO zebrafish paradigms offer a reproducible, ethically advantageous platform for conducting research related to early-onset epilepsy and for antiseizure medication screening targeting this age group.
期刊介绍：
Pharmacological Reports publishes articles concerning all aspects of pharmacology, dealing with the action of drugs at a cellular and molecular level, and papers on the relationship between molecular structure and biological activity as well as reports on compounds with well-defined chemical structures.
Pharmacological Reports is an open forum to disseminate recent developments in: pharmacology, behavioural brain research, evidence-based complementary biochemical pharmacology, medicinal chemistry and biochemistry, drug discovery, neuro-psychopharmacology and biological psychiatry, neuroscience and neuropharmacology, cellular and molecular neuroscience, molecular biology, cell biology, toxicology.
Studies of plant extracts are not suitable for Pharmacological Reports.
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