Pharmacological analysis of zebrafish lphn3.1 morphant larvae suggests that saturated dopaminergic signaling could underlie the ADHD-like locomotor hyperactivity

Lange, Merlin; Froc, Cynthia; Grunwald, Hannah; Norton, William; Bally‐Cuif, Laure

doi:10.1016/j.pnpbp.2018.02.010

Cited by 38 publications

(35 citation statements)

References 50 publications

(82 reference statements)

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“…The aGPCR latrophilin 3 (ADGRL3, human homolog) was recently associated with an increased risk of attention-deficit/hyperactivity disorder (ADHD) and substance use in human genetic studies 3 , 4 . Gene knockdown of ADGRL3 homologs in flies 5 , fish 6 , 7 , rat 8 and mouse 9 has been associated with a pan-species hyperlocomotor phenotype, as well as dysregulation of dopamine signaling. Thus, ADGRL3 may offer a novel target for modulating dopamine signaling, with important therapeutic implications for the treatment of ADHD and other neuropsychiatric disorders that involve dopamine dysfunction, such as schizophrenia.…”

Section: Introductionmentioning

confidence: 99%

G12/13 is activated by acute tethered agonist exposure in the adhesion GPCR ADGRL3

et al. 2020

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The adhesion GPCR latrophilin 3 (ADGRL3) has been associated with increased risk of attention-deficit/hyperactivity disorder (ADHD) and substance use in human genetic studies. Knockdown in multiple species leads to hyperlocomotion and altered dopamine signaling. Thus, ADGRL3 is a potential target for treatment of neuropsychiatric disorders that involve dopamine dysfunction, but its basic signaling properties are poorly understood. Identification of adhesion GPCR signaling partners has been limited by lack of tools to acutely activate these receptors in living cells. Here, we designed a novel acute activation strategy to characterize ADGRL3 signaling by engineering a receptor construct in which we could trigger acute activation enzymatically. Using this assay, we found that ADGRL3 signals through G12/G13 and Gq, with G12/13 the most robustly activated. Gα12/13 is a new player in ADGRL3 biology, opening up unexplored roles for ADGRL3 in the brain. Our methodological advancements should be broadly useful in adhesion GPCR research.

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Section: Introductionmentioning

confidence: 99%

G12/13 is activated by acute tethered agonist exposure in the adhesion GPCR ADGRL3

et al. 2020

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“…There was no statistically significant interaction between treatment and time ( F 25,1245 = 1.39, P = 0.096). Because of this reduction in locomotor activity over time, supported by other reports, 69‐71 we repeated the analysis on the first 30 minutes only. The repeated‐measure ANOVA showed a significant main effect of the treatment ( F 5,249 = 2.565, P = 0.028).…”

Section: Resultsmentioning

confidence: 74%

Impacts of bisphenol A analogues on zebrafish post‐embryonic brain

Coumailleau

Trempont

Pellegrini

et al. 2020

J Neuroendocrinology

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Bisphenol A (BPA) is a widely studied and well‐recognised endocrine‐disrupting chemical, and one of the current issues is its safe replacement by various analogues. Using larva zebrafish as a model, the present study reveals that moderate and chronic exposure to BPA analogues such as bisphenol S, bisphenol F and bisphenol AF may also affect vertebrate neurodevelopment and locomotor activity. Several parameters of embryo‐larval development were investigated, such as mortality, hatching, number of mitotically active cell, as defined by 5‐bromo‐2'‐deoxyuridine incorporation and proliferative cell nuclear antigen labelling, aromatase B protein expression in radial glial cell and locomotor activity. Our results show that exposure to several bisphenol analogues induced an acceleration of embryo hatching rate. At the level of the developing brain, a strong up‐regulation of the oestrogen‐sensitive Aromatase B was also detected in the hypothalamic region. This up‐regulation was not associated with effects on the numbers of mitotically active progenitors nor differentiated neurones in the preoptic area and in the nuclear recessus posterior of the hypothalamus zebrafish larvae. Furthermore, using a high‐throughput video tracking system to monitor locomotor activity in zebrafish larvae, we show that some bisphenol analogues, such as bisphenol AF, significantly reduced locomotor activity following 6 days of exposure. Taken together, our study provides evidence that BPA analogues can also affect the neurobehavioural development of zebrafish.

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“…For example, in other zebrafish models of chemical-induced hyperactivity, exposed animals also showed impaired learning and memory (Chen et al 2012;Saili et al 2012;Knecht et al 2017). Hyperactivity has also been observed in various zebrafish models of intellectual disability (Kim et al 2014;Chen et al 2018;Lange et al 2018). Therefore, it may be that the hyperactivity observed in zebrafish exposed to Ag-NPs is in fact an impaired acclimation to the dark 2 period.…”

Section: Discussionmentioning

confidence: 99%

Developmental exposure to silver nanoparticles at environmentally relevant concentrations alters swimming behavior in zebrafish (Danio rerio)

González

Carty

Tran

et al. 2018

Enviro Toxic and Chemistry

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Silver nanoparticles (Ag-NP) are ubiquitous in household and medical products because of their antimicrobial activity. A consequence of the high volume of Ag-NP production and usage is increased amounts of Ag-NPs released into the environment. Their small size (between 1–100 nanometers) results in unique physiochemical properties that may increase toxicity relative to their bulk counterpart. Therefore, the goal of this study is to assess the potential toxicity of environmentally relevant concentrations of Ag-NPs in zebrafish (Danio rerio). Wild-type tropical 5D zebrafish embryos were exposed to Ag-NPs from 4 to 120 hours post fertilization (hpf) at 0.03, 0.1, 0.3, 1, 3 ppm (mg/L). Inductively-coupled plasma mass spectrometry (ICP-MS) confirmed concentration-dependent uptake of Ag into zebrafish as well as bioaccumulation over time. A morphological assessment revealed no significant hatching impairment, morphological abnormalities, or mortality at any concentration or time point examined. However, assessment of photomotor behavior at 3 days post fertilization (dpf) revealed significant hyperactivity in the 0.3, 1, and 3 ppm Ag-NP treatment groups. At 4 dpf, significant hyperactivity was observed only in the 3 ppm treatment group, while 5 dpf larvae exposed to Ag-NPs displayed no significant abnormalities in photomotor behavior. These findings suggest that non-teratogenic concentrations of Ag-NPs are capable of causing transient behavioral changes during development.

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Pharmacological analysis of zebrafish lphn3.1 morphant larvae suggests that saturated dopaminergic signaling could underlie the ADHD-like locomotor hyperactivity

Cited by 38 publications

References 50 publications

G12/13 is activated by acute tethered agonist exposure in the adhesion GPCR ADGRL3

G12/13 is activated by acute tethered agonist exposure in the adhesion GPCR ADGRL3

Impacts of bisphenol A analogues on zebrafish post‐embryonic brain

Developmental exposure to silver nanoparticles at environmentally relevant concentrations alters swimming behavior in zebrafish (Danio rerio)

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