Sustained behavioral effects of lithium exposure during early development in zebrafish: Involvement of the Wnt-β-catenin signaling pathway

Nery, Laura Roesler; Eltz, Natalia Silva; Martins, L. Borges; Guerim, Laura D.; Pereira, Talita Carneiro Brandão; Bogo, Maurı́cio Reis; Vianna, Mônica Ryff Moreira Roca

doi:10.1016/j.pnpbp.2014.04.011

Cited by 22 publications

(24 citation statements)

References 39 publications

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“…To evaluate Wnt signaling in hearts with endocardial Notch inhibition, we used qPCR to measure the relative abundances of three previously validated Wnt targets in 5 dpa control and Tg(DNMAML) EC hearts. While one target, mycn ( Alexander et al, 2014 ), showed highly variable expression between replicates, the other two targets, axin2 ( Alexander et al, 2014 ) and ccnd1 ( Nery et al, 2014 ), were found to be significantly increased in injured Tg(DN-MAML) EC hearts ( Figure S6A ), suggesting that endocardial Notch signaling functions to restrain Wnt signaling during heart regeneration.…”

Section: Resultsmentioning

confidence: 99%

Endocardial Notch Signaling Promotes Cardiomyocyte Proliferation in the Regenerating Zebrafish Heart through Wnt Pathway Antagonism

et al. 2019

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SUMMARY Previous studies demonstrate that the regenerative zebrafish heart responds to injury by upregulating Notch receptors in the endocardium and epicardium. Moreover, global suppression of Notch activity following injury impairs cardiomyocyte proliferation and induces scarring. However, the lineage-specific requirements for Notch signaling and full array of downstream targets remain unidentified. Here, we demonstrate that inhibition of endocardial Notch signaling following ventricular amputation compromises cardiomyocyte proliferation and stimulates fibrosis. RNA sequencing uncovered reduced levels of two transcripts encoding secreted Wnt antagonists, Wif1 and Notum1b, in Notch-suppressed hearts. Like Notch receptors, wif1 and notum1b are induced following injury in the endocardium and epicardium. Small-molecule-mediated activation of Wnt signaling is sufficient to impair cardiomyocyte proliferation and induce scarring. Last, Wnt pathway suppression partially restored cardiomyocyte proliferation in hearts experiencing endocardial Notch inhibition. Taken together, our data demonstrate that Notch signaling supports cardiomyocyte proliferation by dampening myocardial Wnt activity during zebrafish heart regeneration.

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Section: Resultsmentioning

confidence: 99%

Endocardial Notch Signaling Promotes Cardiomyocyte Proliferation in the Regenerating Zebrafish Heart through Wnt Pathway Antagonism

et al. 2019

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“…Righting reflex, cliff avoidance, rotating reflex, locomotor activity test Delayed eye opening. Inhibitory dose-dependent effect on sensory motor reflexes and locomotor activity Nery (2014) [ 31 ] Zebrafish/Daniorerio 0.05 mM, 0.5 mM, 5 mM System water G3 10 days Locomotor activity Dose-dependent locomotor deficit s.c. subcutaneous, n.r. not reported, G gestation day, PND postnatal day, SW Swiss Webster, SD Sprague–Dawley, W Wistar …”

Section: Resultsmentioning

confidence: 99%

“…Whether these developmental delays were caused by prenatal or early postnatal exposure to lithium could not be determined. Nery et al [ 31 ] studied the behavioural effects of lithium exposure on the development of zebrafish embryos and reported decreased locomotion compared to non-exposed embryos. Additionally, several studies have replicated a delay in eye opening [ 29 , 30 , 32 ] and decreased avoidance behaviour [ 32 , 33 ] in mice and rats exposed to lithium during gestation and/or lactation.…”

Section: Lithiummentioning

confidence: 99%

Long-term neurodevelopmental consequences of intrauterine exposure to lithium and antipsychotics: a systematic review and meta-analysis

Poels

Schrijver

Kamperman

et al. 2018

Eur Child Adolesc Psychiatry

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Lithium and antipsychotics are often prescribed to treat bipolar disorder or psychotic disorders in women of childbearing age. Little is known about the consequences of these medications during pregnancy for the developing child. The objective of this article is to systematically review findings from preclinical and clinical studies that have examined the neurodevelopmental consequences of intrauterine exposure to lithium and antipsychotics. A systematic search was performed in Embase, Medline, Web of Science, PsychINFO, Cochrane, and Google Scholar. Clinical and experimental studies were selected if they investigated neurodevelopment of offspring exposed to lithium or antipsychotics during gestation. Quality of clinical and preclinical studies was assessed by the Newcastle–Ottawa Scale and the SYRCLE’s risk of Bias tool, respectively. In total, 73 studies were selected for qualitative synthesis and three studies were selected for quantitative synthesis. Of preclinical studies, 93% found one or more adverse effects of prenatal exposure to antipsychotics or lithium on neurodevelopment or behaviour. Only three clinical cohort studies have investigated the consequences of lithium exposure, all of which reported normal development. In 66% of clinical studies regarding antipsychotic exposure, a transient delay in neurodevelopment was observed. The relative risk for neuromotor deficits after in utero exposure to antipsychotics was estimated to be 1.63 (95% CI 1.22–2.19; I2 = 0%). Preclinical studies suggest long-term adverse neurodevelopmental consequences of intrauterine exposure to either lithium or antipsychotics. However, there is a lack of high-quality clinical studies. Interpretation is difficult, since most studies have compared exposed children with their peers from the unaffected population, which did not allow correction for potential influences regarding genetic predisposition or parental psychiatric illness.Electronic supplementary materialThe online version of this article (10.1007/s00787-018-1177-1) contains supplementary material, which is available to authorized users.

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“…The following drugs were used in this study: lithium carbonate (Tocris cat. number #4740) used at a final concentration of 0.05, 0.5 and 5 mM (Nery et al, 2014); and ethanol (Fisher Scientific cat. number #10342652) used at a final concentration of 0.05%, 0.15% and 0.25% v/v (Fontana et al, 2016).…”

Section: Drug Treatmentmentioning

confidence: 99%

Automatic quantification of juvenile zebrafish aggression

Gutiérrez

Vacca

Pons

et al. 2018

Journal of Neuroscience Methods

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Sustained behavioral effects of lithium exposure during early development in zebrafish: Involvement of the Wnt-β-catenin signaling pathway

Cited by 22 publications

References 39 publications

Endocardial Notch Signaling Promotes Cardiomyocyte Proliferation in the Regenerating Zebrafish Heart through Wnt Pathway Antagonism

Endocardial Notch Signaling Promotes Cardiomyocyte Proliferation in the Regenerating Zebrafish Heart through Wnt Pathway Antagonism

Long-term neurodevelopmental consequences of intrauterine exposure to lithium and antipsychotics: a systematic review and meta-analysis

Automatic quantification of juvenile zebrafish aggression

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