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Pilocarpine Induced Behavioral and Biochemical Alterations in Chronic Seizure-Like Condition in Adult Zebrafish.

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-?, IL-1, BDNF, CREB-1, and NPY; whereas decreased expression of NF-?B 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.

SUBMITTER: Paudel YN

PROVIDER: S-EPMC7178024 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Pilocarpine Induced Behavioral and Biochemical Alterations in Chronic Seizure-Like Condition in Adult Zebrafish.

Paudel Yam Nath YN Kumari Yatinesh Y Abidin Syafiq Asnawi Zainal SAZ Othman Iekhsan I Shaikh Mohd Farooq MF

International journal of molecular sciences 20200403 7

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 dise ...[more]

PMID: 32260203

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Project description:According to the developmental origins of health and disease (DOHaD) hypothesis, exposure to environmental stressors during early development can cause genetic, epigenetic, or functional changes in tissues that increase disease risk later in life. Atrazine (ATZ) is a commonly used pesticide that frequently contaminates rural and urban water sources at levels above the 3 ppb maximum contaminant level set by the US Environmental Protection Agency. Exposure to ATZ is linked to endocrine disruption, cancer, changes in genome methylation, and alterations in neurochemistry and behavior. This study tests the hypothesis that embryonic exposure to ATZ results in sex-specific changes in behavior, the adult brain transcriptome, and adult body and brain pathology, according to the DOHaD hypothesis. Zebrafish (Danio rerio) embryos were exposed to 0, 0.3, 3, or 30 ppb (ppb; µg/L) ATZ during the period from fertilization through 72 hours post fertilization (hpf), and then were rinsed and raised to maturity with no further exposure. At 9 months post fertilization (mpf), a novel tank test, a light-dark box, and an open field test evaluated adult behavior. Transcriptomic analysis investigated ATZ related differences in gene expression and the brain was evaluated histopathologically for morphometric alterations in the area of the dorsal telencephalon, posterior tuberculum, and raphe populations. At 14 mpf, the body length, weight, and brain weight was measured to evaluate effects of ATZ on mature body and brain size. The 9 mpf adult behavioral tests found non-monotonic, sex-specific behavior changes, with male zebrafish having decreased activity and female zebrafish having increased signs of anxiety. Transcriptomic analysis identified sex-specific alterations, with females having altered expression of genes in pathways related to cancer and organismal injury and males having altered gene expression in organismal development and reproductive system development and function pathways. Morphometric analysis identified a decreased number of cells in male raphe populations and adult zebrafish also had non-monotonic, sex-specific alterations in body length, body weight, and brain weight. This results suggests that developmental exposure to ATZ does cause sex-specific alterations in adult neural function.

Dataset Information

Pilocarpine Induced Behavioral and Biochemical Alterations in Chronic Seizure-Like Condition in Adult Zebrafish.

Publications

Pilocarpine Induced Behavioral and Biochemical Alterations in Chronic Seizure-Like Condition in Adult Zebrafish.

Similar Datasets

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