Diazepam and Its Disinfection Byproduct Promote the Early Development of Nervous System in Zebrafish Embryos

The widely used diazepam, as central nervous system inhibitor, has found to be ubiquitous in surface water and drinking water. Moreover, a series of byproducts such as 2-methylamino-5-chlorobenzophenone (MACB) were generated after the chlorine disinfection process. However, little information is available about the neurobiological effects of these emerging chemicals at low doses, especially on infants and children. Here, we exposed zebrafish (Danio rerio) embryos to diazepam and MACB at 0.05, 0.5, and 5 nM, which were equivalent to environmental levels. Both diazepam and MACB increased the somite number and promoted nervous development of transgenic zebrafish [Tg (elavl3: EGFP) larvae] at 72 hours postfertilization ( hpf). Both diazepam and MACB also disrupted the homeostasis of adenosine monophosphate, valine, methionine, and fumaric acid in zebrafish embryos at 12 hpf. Additionally, the locomotor behavior activity of zebrafish was significantly enhanced after 120-hour sustained exposure to diazepam or MACB. Moreover, the mRNA expression levels of oct4, sox2, and nanog, modulating the pluripotency and self-renewal, were upregulated by diazepam and MACB in zebrafish embryo. Altogether, diazepam and MACB stimulate developmental neurogenesis and may induce neuronal excitotoxicity at quite low doses. These results indicated that the chronic exposure to psychoactive drugs may pose a potential risk to the development of the nervous system in infancy.

Download Full-text

Neural selective activation and temporal regulation of a mammalian GAP-43 promoter in zebrafish

Development ◽

10.1242/dev.120.7.1767 ◽

1994 ◽

Vol 120 (7) ◽

pp. 1767-1775 ◽

Cited By ~ 3

Author(s):

E. Reinhard ◽

E. Nedivi ◽

J. Wegner ◽

J.H. Skene ◽

M. Westerfield

Keyword(s):

Nervous System ◽

Embryonic Development ◽

Marker Gene ◽

Transgenic Zebrafish ◽

Zebrafish Embryos ◽

Neural Cells ◽

Cis Acting ◽

Temporal Regulation ◽

Functional Conservation ◽

The Central Nervous System

Neurons throughout the vertebrate nervous system selectively activate the gene for a growth cone component, GAP-43, during embryonic development, and then decrease its expression abruptly as they form synapses. Distal interruption of mature axons in the central nervous system (CNS) of fish and amphibians, but not in the mammalian CNS reverses the developmental down-regulation of GAP-43 expression. To explore functional conservation and divergence of cis-acting elements that regulate expression of the GAP-43 gene, we studied activation, in transgenic zebrafish embryos, of mammalian GAP-43 genomic sequences fused to a marker gene. The DNA fragments containing the GAP-43 promoter, including a short fragment of 386 base pairs, were preferentially activated in the embryonic fish nervous system at times when extensive neuronal differentiation and neurite outgrowth take place. After 2 days of development, expression of the mammalian transgenes was specifically downregulated in the fish spinal cord but increased in more rostral regions of the CNS. This expression pattern was well correlated with the regulation of the endogenous fish GAP-43 gene revealed by in situ hybridization. Elements of the mammalian gene located a substantial distance upstream of the minimal promoter directed additional expression of the marker gene in a specific set of non-neural cells in zebrafish embryos. Our results indicate that cis-acting elements of the GAP-43 gene, and signaling pathways controlling these elements during embryonic development, have been functionally conserved in vertebrate evolution.

Download Full-text

Fate of sulfamethoxazole and potential formation of haloacetic acids during chlorine disinfection process in aquaculture water

Environmental Research ◽

10.1016/j.envres.2021.111958 ◽

2021 ◽

pp. 111958

Author(s):

Xiaoyi Lou ◽

Zhiyuan Liu ◽

Changling Fang ◽

Yunyu Tang ◽

Jie Guan ◽

...

Keyword(s):

Haloacetic Acids ◽

Chlorine Disinfection ◽

Disinfection Process ◽

Potential Formation ◽

Aquaculture Water

Download Full-text

Fluorescent protein expression driven by her4 regulatory elements reveals the spatiotemporal pattern of Notch signaling in the nervous system of zebrafish embryos

Developmental Biology ◽

10.1016/j.ydbio.2006.10.020 ◽

2007 ◽

Vol 301 (2) ◽

pp. 555-567 ◽

Cited By ~ 92

Author(s):

Sang-Yeob Yeo ◽

MinJung Kim ◽

Hyung-Seok Kim ◽

Tae-Lin Huh ◽

Ajay B. Chitnis

Keyword(s):

Nervous System ◽

Protein Expression ◽

Notch Signaling ◽

Fluorescent Protein ◽

Regulatory Elements ◽

Spatiotemporal Pattern ◽

Zebrafish Embryos

Download Full-text

Preparation of Transgenic Zebrafish Embryos for Imaging the Developing Retina

Cold Spring Harbor Protocols ◽

10.1101/pdb.prot073536 ◽

2013 ◽

Vol 2013 (3) ◽

pp. pdb.prot073536 ◽

Cited By ~ 3

Author(s):

Patricia Jusuf ◽

William A. Harris ◽

Lucia Poggi

Keyword(s):

Transgenic Zebrafish ◽

Zebrafish Embryos

Download Full-text

Influence of ionizing radiations on the development of the nervous system

Acta geneticae medicae et gemellologiae ◽

10.1017/s1120962300013093 ◽

1967 ◽

Vol 16 (3) ◽

pp. 275-309 ◽

Cited By ~ 2

Author(s):

W. Geets

Keyword(s):

Nervous System ◽

Cerebral Cortex ◽

Research Work ◽

Low Doses ◽

Embryonic Period ◽

Clinical Observations ◽

Functional Maturation ◽

Maturation Stages ◽

Mother Cells ◽

Ionizing Radiations

SUMMARYThe first cellular differentiation in the process of segmentation leads to the embryonic period, the major organogenetic period for the nervous system. In man, it appears between the second and the eighth week after conception.During the foetal and perinatal periods, the nervous organization mainly develops at the cerebellum and cerebral cortex levels. The cerebrum functional maturation continues well beyond birth.Neuroblasts are the most widespread mother-cells in the developing nervous system during the embryonic period, but some are still to be found after birth.Animal experiment has demonstrated that ionizing radiations were able to disorganize neurogenesis in any of its maturation stages, even at very low doses. It is possible to establish a chronological table showing the anatomical or functional deformities in relation with the embryonic age at which rays have been given.It appears that in man the most dangerous period is between the beginning of the second and the end of the eighth week after conception. At that moment, pregnancy is often ignored and a dose of 20 to 40 r is sufficient to entail serious damages, such as microcephaly, protrusions of the brain or mental retardation. On drawing near to birth the foetal or neonatal nervous system of rodents or primates is still radiosensitive, especially at the cerebral cortex level and the consequences will be of a neurophysiologic or psychosensorial nature. Certain embryopathies or neurologic alterations would only be apparent in subsequent generations, following mutations induced into the mother-cells of the nervous system. Genetic deformities of the nervous system can also result from moderate irradiations of the gonads.Further to the precise experimental research work on the radiovulnerability of the embryonic or foetal nervous system of the animal, certain clinical observations are presented, which lead to similar conclusions.The atomic bombardments have caused numerous neurological trouble among the children who had been irradiated in utero. And the genetic effects are not yet perfectly known to-date.This set of experimental and clinical data must prompt us to be very careful when using ionizing radiations, even at low doses, in pregnant women and newborn.

Download Full-text

Toxicity and teratogenicity evaluation of hydroethanolic extract of momordica charantia fruit using zebrafish (DANIO RERIO) embryos model

International Journal of Research in Pharmaceutical Sciences ◽

10.26452/ijrps.v10ispl1.1720 ◽

2019 ◽

Vol 10 (SPL1) ◽

Author(s):

Noor Izati Abd Aziz ◽

Vikneswari Perumal ◽

Suganya Murugesu ◽

Qamar Uddin Ahmed ◽

Bisha Fathamah Uzir ◽

...

Keyword(s):

Danio Rerio ◽

Crude Extract ◽

Momordica Charantia ◽

Spinal Curvature ◽

Zebrafish Embryos ◽

Chemical Toxicity ◽

Active Constituent ◽

Hydroethanolic Extract ◽

Danio Rerio Embryos

The use of zebrafish vertebrate model in vivo analysis of the drug toxicity and efficacy, chemical toxicity, and safety is increasing in recent researches. Momordica charantia Linn (Cucurbitaceae) has been traditionally claimed for its many protective roles. However, the development of toxicity effect may cause morphological abnormalities by using an embryo of zebrafish (Danio Rerio) is unknown. Hence, this study was designed to determine the toxicity and teratogenic effect of hydroethanolic extract of M. charantia fruit using Zebrafish (Danio Rerio) embryos. The crude extract was prepared from the fruit of M. charantia using 80% hydroethanolic solvent. The zebrafish embryos were exposed to serial dilution of crude extract. The active constituent was analyzed using gas chromatography coupled with mass spectrophotometry (GC-MS) Momordica charantia Linn (Cucurbitaceae) has been widely commercialized based on traditional usage as an antidiabetic product. The current study has shown the toxic effects of the M. charantia fruit extract on the developing zebrafish embryos, and the median lethal concentration (LC50) was calculated to be 725.90 mg/L at 48 hpt. The observed effects are dependent on the time of exposure and concentrations of the extract. At higher concentration, the extract causes some morphological defects such as less pigmentation, dented tail, spinal curvature, oedema, reduced hatchability, and growth retardation, that indicates the presence of toxicant(s). Based on the GC-MS profiling, some of the compounds identified in the hydroethanolic extract, such as propanedioic acid and glutamine, may have caused the teratogenic effects to the embryos. Further research on the M. charantia fruit's metabolites should be carried out prior to any nutraceutical or pharmaceutical application.

Download Full-text

Myelination of the motor nerves in the peripheral nervous system of zebrafish embryos

Frontiers in Cellular Neuroscience ◽

10.3389/conf.fncel.2016.36.00171 ◽

2016 ◽

Vol 10 ◽

Author(s):

Lee Dong-Won ◽

Kim Suhyun ◽

Kim Eunmi ◽

Jeong Inyoung ◽

Kim Hwan-Ki ◽

...

Keyword(s):

Nervous System ◽

Peripheral Nervous System ◽

Zebrafish Embryos ◽

Motor Nerves

Download Full-text

Cardioluminescence in transgenic zebrafish embryos: a calcium imaging tool to study drug effects and pathological modeling

10.1101/2021.05.06.442917 ◽

2021 ◽

Author(s):

Manuel Vicente ◽

Jussep Salgado-Almario ◽

Michelle M. Collins ◽

Antonio Martinez-Sielva ◽

Masafumi Minoshima ◽

...

Keyword(s):

Signal To Noise Ratio ◽

Light Output ◽

Drug Effects ◽

Study Drug ◽

Transgenic Zebrafish ◽

Zebrafish Embryos ◽

Cardiovascular Research ◽

Imaging Tool ◽

Adrenergic Blocker

The zebrafish embryo has emerged as an excellent model in cardiovascular research. The existing techniques to monitor Ca2+ in the heart based on fluorescent Ca2+ biosensors are limited due to phototoxicity and photobleaching. To overcome these issues, we have used bioluminescence. We generated a transgenic line expressing GFP-Aequorin in the heart, Tg(cmlc2:GA), and optimized an in vivo aequorin reconstitution protocol to improve the luminescence capacity. This allowed imaging Ca2+ in long duration recordings in embryos of 3 to 5 days post-fertilization. The analogs diacetyl h-coelenterazine and f-coelenterazine enhanced the light output and signal-to-noise ratio from the embryos. With this cardioluminescence model, we monitored the time-averaged Ca2+ levels and beat-to-beat Ca2+ oscillations. Changes in Ca2+ levels were observed by incubation with BayK8644, an L-type Ca2+ channel agonist, the channel blocker nifedipine, and β-adrenergic blocker propranolol. Treatment of zebrafish embryos with terfenadine for 24 hours has been proposed as a model of heart failure. Tg(cmlc2:GA) embryos treated with terfenadine showed a 2:1 atrioventricular block and a decrease in the ventricular Ca2+ levels.

Download Full-text