Zebrafish, a biological model for pharmaceutical research for the management of anxiety

Chahardehi, Amir Modarresi; Hosseini, Yasaman; Mahdavi, Seyed Mohammad; Naseh, Iman

doi:10.1007/s11033-023-08263-1

Cited by 6 publications

(2 citation statements)

References 90 publications

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“…Zebrafish ( Danio rerio ) is an invaluable model organism for studying vertebrate development and genetics, offering advantages such as rapid development, high reproductive capacity, advanced genetic modification tools, and transparency of embryos for internal morphology observation 20 . With significant genetic similarities to humans and the ability to easily modulate gene expression, zebrafish has emerged as an ideal model for studying human diseases in various fields such as ALS 21 , cancer biology and precision medicine 22 , anxiety 23 , and neurodegenerative disease 24 . Specifically, zebrafish’s suitability for investigating muscular dystrophy stems from its easily mutating disease-causing genes, imaging intact muscle tissue, and using for therapeutic screening 25 .…”

Section: Introductionmentioning

confidence: 99%

Creatine and l-carnitine attenuate muscular laminopathy in the LMNA mutation transgenic zebrafish

Pan,

Wang,

Hsiao

et al. 2024

Sci Rep

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Lamin A/C gene (LMNA) mutations contribute to severe striated muscle laminopathies, affecting cardiac and skeletal muscles, with limited treatment options. In this study, we delve into the investigations of five distinct LMNA mutations, including three novel variants and two pathogenic variants identified in patients with muscular laminopathy. Our approach employs zebrafish models to comprehensively study these variants. Transgenic zebrafish expressing wild-type LMNA and each mutation undergo extensive morphological profiling, swimming behavior assessments, muscle endurance evaluations, heartbeat measurement, and histopathological analysis of skeletal muscles. Additionally, these models serve as platform for focused drug screening. We explore the transcriptomic landscape through qPCR and RNAseq to unveil altered gene expression profiles in muscle tissues. Larvae of LMNA(L35P), LMNA(E358K), and LMNA(R453W) transgenic fish exhibit reduced swim speed compared to LMNA(WT) measured by DanioVision. All LMNA transgenic adult fish exhibit reduced swim speed compared to LMNA(WT) in T-maze. Moreover, all LMNA transgenic adult fish, except LMNA(E358K), display weaker muscle endurance than LMNA(WT) measured by swimming tunnel. Histochemical staining reveals decreased fiber size in all LMNA mutations transgenic fish, excluding LMNA(WT) fish. Interestingly, LMNA(A539V) and LMNA(E358K) exhibited elevated heartbeats. We recognize potential limitations with transgene overexpression and conducted association calculations to explore its effects on zebrafish phenotypes. Our results suggest lamin A/C overexpression may not directly impact mutant phenotypes, such as impaired swim speed, increased heart rates, or decreased muscle fiber diameter. Utilizing LMNA zebrafish models for drug screening, we identify l-carnitine treatment rescuing muscle endurance in LMNA(L35P) and creatine treatment reversing muscle endurance in LMNA(R453W) zebrafish models. Creatine activates AMPK and mTOR pathways, improving muscle endurance and swim speed in LMNA(R453W) fish. Transcriptomic profiling reveals upstream regulators and affected genes contributing to motor dysfunction, cardiac anomalies, and ion flux dysregulation in LMNA mutant transgenic fish. These findings faithfully mimic clinical manifestations of muscular laminopathies, including dysmorphism, early mortality, decreased fiber size, and muscle dysfunction in zebrafish. Furthermore, our drug screening results suggest l-carnitine and creatine treatments as potential rescuers of muscle endurance in LMNA(L35P) and LMNA(R453W) zebrafish models. Our study offers valuable insights into the future development of potential treatments for LMNA-related muscular laminopathy.

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Section: Introductionmentioning

confidence: 99%

Creatine and l-carnitine attenuate muscular laminopathy in the LMNA mutation transgenic zebrafish

Pan,

Wang,

Hsiao

et al. 2024

Sci Rep

View full text Add to dashboard Cite

show abstract

“…Zebra sh (Danio rerio) is an invaluable model organism for studying vertebrate development and genetics, offering advantages such as rapid development, high reproductive capacity, advanced genetic modi cation tools, and transparency of embryos for internal morphology observation 19 . With signi cant genetic similarities to humans and the ability to easily modulate gene expression, zebra sh has emerged as an ideal model for studying human diseases in various elds such as ALS 20 , cancer biology and precision medicine 21 , anxiety 22 , and neurodegenerative disease 23 . Speci cally, zebra sh's suitability for investigating muscular dystrophy stems from its easily mutating disease-causing genes, imaging intact muscle tissue, and using for therapeutic screening 24 .…”

Section: Introductionmentioning

confidence: 99%

Creatine and L-carnitine attenuate muscular laminopathy in the LMNA mutation transgenic zebrafish

Yuh,

Pan,

Wang

et al. 2023

Preprint

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LMNA gene mutations cause debilitating striated muscle laminopathies, affecting cardiac and skeletal muscles, with limited treatments. This study investigates five LMNA mutations using zebrafish models. Transgenic zebrafish expressing wild-type LMNAand each mutation are extensively profiled for morphology, behavior, and histology, with a focus on skeletal muscles. Drug screening and transcriptomic analysis uncover altered gene expression. Intriguing phenotypes emerge in adult zebrafish with LMNA mutations. LMNA(W520G) variants exhibit a mortality rate within three months. LMNA(A539V) fish exhibit abnormalities in F0 adults and crooked bodies in F1 adults, similar to LMNA(R453W) F1 fish. Larvae of LMNA(L35P), LMNA(E358K), and LMNA(R453W) transgenic fish swim slower than AB(WT) and LMNA(WT) in DanioVision. All LMNA transgenic adult fish, except LMNA(E358K), show reduced swimming speed and muscle endurance compared to AB(WT) in T-maze and swimming tunnel tests. Histochemical staining reveals decreased fiber size in LMNA(L35P), LMNA(E358K), LMNA(R453W), and LMNA(A539V) transgenic fish. Drug screening identifies L-carnitine treatment rescuing muscle endurance in LMNA(L35P) and creatine treatment reversing muscle endurance in LMNA(R453W) zebrafish models. Creatine activates AMPK and mTOR pathways, improving muscle endurance and swimming speed in LMNA(R453W) fish. Transcriptomic profiling reveals upstream regulators and affected genes contributing to motor dysfunction, cardiac anomalies, and ion flux dysregulation in LMNA mutant transgenic fish. These findings mimic clinical manifestations of muscular laminopathies, including dysmorphism, early mortality, decreased fiber size, and muscle dysfunction in zebrafish. Moreover, drug screening suggests L-carnitine and creatine treatments as potential rescuers of muscle endurance in LMNA(L35P) and LMNA(R453W) zebrafish models, offering insights into treating LMNA-related muscular laminopathy.

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Evaluating the potential effects of apigenin on memory, anxiety, and social interaction amelioration after social isolation stress

Mohammadkhanizadeh,

Hosseini,

Nikbakht

et al. 2024

Intl J of Devlp Neuroscience

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Vigorous research confirmed the anti‐inflammatory, antioxidant, and antidementia effects of apigenin (Api). The present study evaluated the beneficial impacts of Api administration on behaviour, brain‐derived neurotrophic factor (BDNF), Interleukin 6 (IL‐6), oxidative stress, and inflammation induced by social isolation (SI) stress in rats. For this purpose, rats underwent a 28‐day SI period followed by a 4‐week oral Api treatment (50 mg/kg/day, PO). On Day 56, behaviour tests were performed, including an elevated plus maze (EPM), Morris water maze (MWM), and three‐chamber social tests. The oxidative stress markers, IL‐6, and BDNF levels were measured in the hippocampus. Our results showed that SI stress caused an increase in anxiety and a decrease in spatial memory, sociability, and social preference index. In addition, SI stress increased hippocampal levels of IL‐6 and malondialdehyde (MDA) content, whereas it reduced the hippocampal BDNF level and superoxide dismutase (SOD) activities. Our study indicated that Api attenuates anxiety and causes improvements in spatial memory and social interaction. These desirable effects of Api might be related to amelioration in the BDNF level, IL‐6, and oxidative stress biomarkers in the hippocampus.

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Zebrafish, a biological model for pharmaceutical research for the management of anxiety

Cited by 6 publications

References 90 publications

Creatine and l-carnitine attenuate muscular laminopathy in the LMNA mutation transgenic zebrafish

Creatine and l-carnitine attenuate muscular laminopathy in the LMNA mutation transgenic zebrafish

Creatine and L-carnitine attenuate muscular laminopathy in the LMNA mutation transgenic zebrafish

Evaluating the potential effects of apigenin on memory, anxiety, and social interaction amelioration after social isolation stress

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