Pilocarpine Induced Behavioral and Biochemical Alterations in Chronic Seizure-Like Condition in Adult Zebrafish
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 m...
Main Authors: | , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
MDPI AG
2020-04-01
|
Series: | International Journal of Molecular Sciences |
Subjects: | |
Online Access: | https://www.mdpi.com/1422-0067/21/7/2492 |
id |
doaj-bd088deee3af482c9e1a70f6b15bca13 |
---|---|
record_format |
Article |
spelling |
doaj-bd088deee3af482c9e1a70f6b15bca132020-11-25T02:26:48ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-04-01212492249210.3390/ijms21072492Pilocarpine Induced Behavioral and Biochemical Alterations in Chronic Seizure-Like Condition in Adult ZebrafishYam Nath Paudel0Yatinesh Kumari1Syafiq Asnawi Zainal Abidin2Iekhsan Othman3Mohd. Farooq Shaikh4Neuropharmacology Research Strength, Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Bandar Sunway, Selangor 47500, MalaysiaNeuropharmacology Research Strength, Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Bandar Sunway, Selangor 47500, MalaysiaLC-MS/MS Laboratory, Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Bandar Sunway, Selangor 47500, MalaysiaNeuropharmacology Research Strength, Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Bandar Sunway, Selangor 47500, MalaysiaNeuropharmacology Research Strength, Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Bandar Sunway, Selangor 47500, MalaysiaEpilepsy 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.https://www.mdpi.com/1422-0067/21/7/2492pilocarpinezebrafishseizurecognitioninflammationproteomics |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yam Nath Paudel Yatinesh Kumari Syafiq Asnawi Zainal Abidin Iekhsan Othman Mohd. Farooq Shaikh |
spellingShingle |
Yam Nath Paudel Yatinesh Kumari Syafiq Asnawi Zainal Abidin Iekhsan Othman Mohd. Farooq Shaikh Pilocarpine Induced Behavioral and Biochemical Alterations in Chronic Seizure-Like Condition in Adult Zebrafish International Journal of Molecular Sciences pilocarpine zebrafish seizure cognition inflammation proteomics |
author_facet |
Yam Nath Paudel Yatinesh Kumari Syafiq Asnawi Zainal Abidin Iekhsan Othman Mohd. Farooq Shaikh |
author_sort |
Yam Nath Paudel |
title |
Pilocarpine Induced Behavioral and Biochemical Alterations in Chronic Seizure-Like Condition in Adult Zebrafish |
title_short |
Pilocarpine Induced Behavioral and Biochemical Alterations in Chronic Seizure-Like Condition in Adult Zebrafish |
title_full |
Pilocarpine Induced Behavioral and Biochemical Alterations in Chronic Seizure-Like Condition in Adult Zebrafish |
title_fullStr |
Pilocarpine Induced Behavioral and Biochemical Alterations in Chronic Seizure-Like Condition in Adult Zebrafish |
title_full_unstemmed |
Pilocarpine Induced Behavioral and Biochemical Alterations in Chronic Seizure-Like Condition in Adult Zebrafish |
title_sort |
pilocarpine induced behavioral and biochemical alterations in chronic seizure-like condition in adult zebrafish |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1661-6596 1422-0067 |
publishDate |
2020-04-01 |
description |
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. |
topic |
pilocarpine zebrafish seizure cognition inflammation proteomics |
url |
https://www.mdpi.com/1422-0067/21/7/2492 |
work_keys_str_mv |
AT yamnathpaudel pilocarpineinducedbehavioralandbiochemicalalterationsinchronicseizurelikeconditioninadultzebrafish AT yatineshkumari pilocarpineinducedbehavioralandbiochemicalalterationsinchronicseizurelikeconditioninadultzebrafish AT syafiqasnawizainalabidin pilocarpineinducedbehavioralandbiochemicalalterationsinchronicseizurelikeconditioninadultzebrafish AT iekhsanothman pilocarpineinducedbehavioralandbiochemicalalterationsinchronicseizurelikeconditioninadultzebrafish AT mohdfarooqshaikh pilocarpineinducedbehavioralandbiochemicalalterationsinchronicseizurelikeconditioninadultzebrafish |
_version_ |
1724845520652861440 |