Estrogen prevents cardiac and vascular failure in the ‘listless’ zebrafish (Danio rerio) developmental model

Allgood, Ottie E.; Hamad, Alia; Fox, Joshua; DeFrank, Anna; Gilley, Ryan; Dawson, Frederick; Sykes, Benjamin G; Underwood, Tarenne J.; Naylor, Rachel C.; Briggs, Ashley A.; Lassiter, Christopher S.; Bell, Wade E.; Turner, James

doi:10.1016/j.ygcen.2013.04.016

Cited by 25 publications

(24 citation statements)

References 33 publications

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“…Figure 5D quantifies calcium wave values for the three fish seen in Figure 5A–C. Specifically it is shown that the spike pattern is repeated every 0.4 s in the ERS treated control fish which equates to a HR of approximately 150 ± 10 beats/minute which is in agreement with current and published data for control fish [13]. ).…”

Section: Resultssupporting

confidence: 86%

“…Specifically, eNOS deprivation resulted in numerous intersegmental vessel misconnections, as well as patchy development or deterioration in the dorsal longitudinal anastomatic vessels and vertebral arteries. These vessels are some of the last to develop in the zebrafish and are thus most sensitive to the various eNOSI manipulations during our study period of 2–4 dpf [13]. In a previous study, we reported similarities in vessel anomalies during development in E2 deprived AI-treated fish, which could be rescued with E2 co-treatment [13].…”

Section: Discussionmentioning

confidence: 79%

“…Specifically, nNOS is expressed early in zebrafish development at 16 to 19 h post fertilization (hpf). Zebrafish are also responsive to nNOS inhibitors (nNOSI), as well as many of the dependent and independent pathway agonists and antagonists [13]. The nNOS isoform is also expressed in the developing zebrafish medulla, a region of the brain that is known to control heart rate [14].…”

Section: Introductionmentioning

confidence: 99%

“…Previous work in our lab has described the “listless” model’ which is initiated by E2 and NO deprivation [13,16,17]. Specifically, both E2 and NO deficiencies cause reduced heart rates and increased arrhythmias, as well as initiating severe sensory-motor deficits.…”

Section: Introductionmentioning

confidence: 99%

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The Relationship between Estrogen and Nitric Oxide in the Prevention of Cardiac and Vascular Anomalies in the Developing Zebrafish (Danio Rerio)

et al. 2016

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It has been known that both estrogen (E2) and nitric oxide (NO) are critical for proper cardiovascular system (CVS) function. It has also been demonstrated that E2 acts as an upstream effector in the nitric oxide (NO) pathway. Results from this study indicate that the use of a nitric oxide synthase (NOS) inhibitor (NOSI) which targets specifically neuronal NOS (nNOS or NOS1), proadifen hydrochloride, caused a significant depression of fish heart rates (HR) accompanied by increased arrhythmic behavior. However, none of these phenotypes were evident with either the inhibition of endothelial NOS (eNOS) or inducible NOS (iNOS) isoforms. These cardiac arrhythmias could also be mimicked by inhibition of E2 synthesis with the aromatase inhibitor (AI), 4-OH-A, in a manner similar to that of nNOSI. In both scenarios, by using an NO donor (DETA-NO) in either NO + nNOSI or E2 + AI co-treatments, fish could be significantly rescued from decreased HR and increased arrhythmias. However, the addition of an NOS inhibitor (L-NAME) to the E2 + AI co-treatment fish prevented the rescue of low heart rates and arrhythmias, which strongly implicates the NO pathway as a downstream E2 targeted molecule for the maintenance of healthy cardiomyocyte contractile conditions in the developing zebrafish. Cardiac arrhythmias could be mimicked by the S-nitrosylation pathway inhibitor DTT (1,4-dithiothreitol) but not by ODQ (1H-[1–3]oxadiazolo[4,3-a]quinoxalin-1-one), the inhibitor of the NO receptor molecule sGC in the cGMP-dependent pathway. In both the nNOSI and AI-induced arrhythmic conditions, 100% of the fish expressed the phenotype, but could be rapidly rescued with maximum survival by a washout with dantrolene, a ryanodine Ca2+ channel receptor blocker, compared to the time it took for rescue using a control salt solution. In addition, of the three NOS isoforms, eNOS was the one most implicated in the maintenance of an intact developing fish vascular system. In conclusion, results from this study have shown that nNOS is the prominent isoform that is responsible, in part, for maintaining normal heart rates and prevention of arrhythmias in the developing zebrafish heart failure model. These phenomena are related to the upstream stimulatory regulation by E2. On the other hand, eNOS has a minimal effect and iNOS has little to no influence on this phenomenon. Data also suggests that nNOS acts on the zebrafish cardiomyocytes through the S-nitrosylation pathway to influence the SR ryanidine Ca2+ channels in the excitation-coupling phenomena. In contrast, eNOS is the prominent isoform that influences blood vessel development in this model.

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Section: Resultssupporting

confidence: 86%

Section: Discussionmentioning

confidence: 79%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The Relationship between Estrogen and Nitric Oxide in the Prevention of Cardiac and Vascular Anomalies in the Developing Zebrafish (Danio Rerio)

et al. 2016

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“…As a vertebrate model organism, zebrafish have long been widely utilised for biomedical research, particularly in neuroscience3536, drug discovery, and developmental and genetic research373839. They present many advantages for the study of human disease and have become an excellent choice for behavioural experiments404142; these advantages include the low maintenance costs, a short reproductive cycle, and rapid and synchronised development.…”

mentioning

confidence: 99%

Behavioural screening of zebrafish using neuroactive traditional Chinese medicine prescriptions and biological targets

Wang

Hou

Sun

et al. 2014

Sci Rep

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The mechanism of the therapeutic action of antidepressants remains uncertain in traditional Chinese medicine (TCM). In this study, we selected 7 classical TCM prescriptions and utilised an automatic video-tracking system to monitor the rest/wake behaviour of larval zebrafish at 4 days post-fertilisation (dpf) for 48 hours. We found that the curative effects of the prescriptions were dose-dependent. K-means clustering was performed according to the shared behavioural phenotypes of the zebrafish. The results revealed that the rest/wake behavioural profiles induced by the same class of prescriptions were similar. A correlation analysis was conducted between the TCM prescriptions and the known compounds. The results showed that the TCM prescriptions correlated well with some well-known compounds. Therefore, we predicted that they may share a similar mechanism of action. This paper describes the first study to combine TCM research with zebrafish rest/wake behaviour in vivo and presents a powerful approach for the discovery of the mechanism of action of TCM prescriptions.

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Using Zebrafish to Analyze the Genetic and Environmental Etiologies of Congenital Heart Defects

Shrestha

Lieberth

Tillman

et al. 2020

Advances in Experimental Medicine and Biology

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Estrogen prevents cardiac and vascular failure in the ‘listless’ zebrafish (Danio rerio) developmental model

Cited by 25 publications

References 33 publications

The Relationship between Estrogen and Nitric Oxide in the Prevention of Cardiac and Vascular Anomalies in the Developing Zebrafish (Danio Rerio)

The Relationship between Estrogen and Nitric Oxide in the Prevention of Cardiac and Vascular Anomalies in the Developing Zebrafish (Danio Rerio)

Behavioural screening of zebrafish using neuroactive traditional Chinese medicine prescriptions and biological targets

Using Zebrafish to Analyze the Genetic and Environmental Etiologies of Congenital Heart Defects

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