Abstract
Epilepsy is a devastating neurological condition exhibited by repeated spontaneous and unpredictable seizures afflicting around 70 million people globally. The basic pathophysiology of epileptic seizures is still elusive, reflecting an extensive need for further research. Developing a novel animal model is crucial in understanding disease mechanisms as well as in assessing the therapeutic target. Most of the pre-clinical epilepsy research has been focused on rodents. Nevertheless, zebrafish disease models are relevant to human disease pathophysiology hence are gaining increased attention nowadays. The current study for the very first time developed a pilocarpine-induced chronic seizure-like condition in adult zebrafish and investigated the modulation in several neuroinflammatory genes and neurotransmitters after pilocarpine exposures. Seizure score analysis suggests that compared to a single dose, repeated dose pilocarpine produces chronic seizure-like effects maintaining an average seizure score of above 2 each day for a minimum of 10 days. Compared to the single dose pilocarpine treated group, there was increased mRNA expression of HMGB1, TLR4, TNF-α, IL-1, BDNF, CREB-1, and NPY; whereas decreased expression of NF-κB was upon the repeated dose of pilocarpine administration. In addition, the epileptic group demonstrates modulation in neurotransmitters levels such as GABA, Glutamate, and Acetylcholine. Moreover, proteomic profiling of the zebrafish brain from the normal and epileptic groups from LCMS/MS quantification detected 77 and 13 proteins in the normal and epileptic group respectively. Summing up, the current investigation depicted that chemically induced seizures in zebrafish demonstrated behavioral and molecular alterations similar to classical rodent seizure models suggesting the usability of adult zebrafish as a robust model to investigate epileptic seizures.
Highlights
Epilepsy is a neurological disorder depicted by the spontaneous and unpredictable occurrence of seizures due to abnormal excessive and synchronous neuronal activity in the brain [1]
[19],developed seizure-like quantified by pattern seizure of scoring for zebrafish (Table pilocarpine-induced seizure has been developed via assessing the swimming pattern of epileptic zebrafish (Table 1)
In the current study we developed a chronic seizure-like condition using pilocarpine in adult zebrafish
Summary
Epilepsy is a neurological disorder depicted by the spontaneous and unpredictable occurrence of seizures due to abnormal excessive and synchronous neuronal activity in the brain [1]. The high mobility group box 1 (HMGB1) is an initiator and amplifier of neuroinflammation and recently emerged as a novel frontier in epileptogenesis due to its plausible contribution to seizure propagation in animal models [5,6]. 22ofof epileptogenesis due to its plausible contribution to seizure propagation in animal models [5,6].
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