Duloxetine ameliorates valproic<scp>acid‐induced</scp>hyperactivity, anxiety‐like behavior, and social interaction deficits in zebrafish

Joseph, Thomson Patrick; Zhou, Fengli; Liu, Sai; Chen, Hanyu; Lin, Stanley L.; Schachner, Melitta

doi:10.1002/aur.2620

Cited by 18 publications

(13 citation statements)

References 78 publications

(109 reference statements)

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“…Percentage of mortality profoundly increased across concentrations, denoting contradictory outcomes with the study by Chen et al (2018), which reported zero embryonic mortality for all tested concentrations (0, 5, 50, 500, 1000, and 1500 μM). However, the parallel trend concluded by Joseph et al (2022) and Dwivedi et al (2019) supported the data of this study. Additionally, VPA levels started to decrease following 48 h of treatment, suggesting that it was absorbed by the embryos (Zimmermann et al, 2015).…”

Section: Discussionsupporting

confidence: 92%

Toxicity and teratogenicity effects of valproic acid on zebrafish (Danio rerio) embryos in relation to autism spectrum disorder

Saleh Hodin,

Chong,

Bakar

et al. 2023

Birth Defects Research

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Valproic acid (VPA) is a widely prescribed antiepileptic drug with various medicinal efficacies. Accumulated evidence implied that prenatal exposure to VPA is highly associated with autism spectrum disorder (ASD). In this study, the zebrafish were exposed to a set of VPA concentrations (0, 5, 10, 20, 40, 80, 160, 320, 640, 1280, and 2560 μM) at 5 h post fertilization (hpf) to 120 hpf. The adverse effects of VPA were extensively studied through the evaluations on the mortality, heartbeats, spontaneous tail coiling, and hatching rate. Morphological observations were conducted at 120 hpf, following the exposure termination. Basic locomotor responses and anxiety‐like behavioral alterations evaluated for behavioral impairments are the hallmark feature of ASD. The exposure to VPA at teratogenic concentrations reduced the aforementioned parameters in a dose‐dependent manner (p ≤ .05). At the selected non‐teratogenic concentrations of VPA, the treated larvae demonstrated profound alterations of basic locomotor responses. No significant changes of anxiety and thigmotactic behaviors were observed on the VPA‐treated fish compared to the control (p ≥ .005). This study depicted that embryonic zebrafish exposure to VPA produced significant toxicity and teratogenicity effects as well as the alterations of basic behavioral responses. Overall, this study provides a fundamental insight of the toxicity effects at morphological and behavioral levels to facilitate the understanding of ASD mechanisms at different molecular levels.

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Section: Discussionsupporting

confidence: 92%

Toxicity and teratogenicity effects of valproic acid on zebrafish (Danio rerio) embryos in relation to autism spectrum disorder

Saleh Hodin,

Chong,

Bakar

et al. 2023

Birth Defects Research

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“…Indeed, when applied in spinal cord injury models as a recombinant glycoprotein or when overexpressed by adeno-associated virus in stem cell-derived neural Biomolecules 2022, 12, 439 2 of 16 aggregates, Schwann cells and radial glial cells, L1 accelerated remyelination and improved axonal regrowth/sprouting/sparing proximal, distal and across the lesion site [9][10][11][12]. In addition, L1 ameliorated the severe consequences of injury in experimental models of neurodegenerative diseases in vitro and in vivo [13][14][15][16][17]. Since the viral delivery of L1, application of recombinant L1, and injection of stem cells overexpressing L1 are expected to meet difficulties in translation to therapy, libraries of small organic molecules were screened for compounds that structurally and functionally mimic L1, and several molecules were found to act as L1 agonistic mimetics [18].…”

Section: Introductionmentioning

confidence: 99%

Antagonistic L1 Adhesion Molecule Mimetic Compounds Inhibit Glioblastoma Cell Migration In Vitro

et al. 2022

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Cell adhesion molecule L1 is a cell surface glycoprotein that promotes neuronal cell migration, fosters regeneration after spinal cord injury and ameliorates the consequences of neuronal degeneration in mouse and zebrafish models. Counter-indicative features of L1 were found in tumor progression: the more L1 is expressed, the more tumor cells migrate and increase their metastatic potential. L1′s metastatic potential is further evidenced by its promotion of epithelial–mesenchymal transition, endothelial cell transcytosis and resistance to chemo- and radiotherapy. These unfortunate features are indicated by observations that cells that normally do not express L1 are induced to express it when becoming malignant. With the aim to ameliorate the devastating functions of L1 in tumors, we designed an alternative approach to counteract tumor cell migration. Libraries of small organic compounds were screened using the ELISA competition approach similar to the one that we used for identifying L1 agonistic mimetics. Whereas in the former approach, a function-triggering monoclonal antibody was used for screening libraries, we here used the function-inhibiting monoclonal antibody 324 that reduces the migration of neurons. We now show that the L1 antagonistic mimetics anagrelide, 2-hydroxy-5-fluoropyrimidine and mestranol inhibit the migration of cultured tumor cells in an L1-dependent manner, raising hopes for therapy.

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“…There were no statistical differences in the average swimming speed among all treatment groups. Behaviors such as social interactions might have higher sensitivity to the effects of anxiolytics and antidepressants than the usual metric of swimming speed of fish (Bencan et al, 2009; Joseph et al, 2022; Takai et al, 2022). Hence we suggest that the response to an image of a predator fish can be a suitable parameter for assessing the effect of anxiolytics on fish behavior.…”

Section: Resultsmentioning

confidence: 99%

Peek‐A‐Boo Test: A Simple Test for Assessing the Effect of Anxiolytics on Fish Behavior

Takai¹,

Izumi²,

Motoyama³

et al. 2023

Enviro Toxic and Chemistry

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The potential of pharmaceuticals and personal‐care products to alter the behavior of aquatic organisms is a growing concern. To assess the actual effect of these substances on aquatic organisms, a simple but effective behavioral test is required. In this study, we devised a simple behavioral test (peek‐a‐boo test) to assess the effect of anxiolytics on the behavior of a model fish (medaka, Oryzias latipes). In the peek‐a‐boo test, we investigated the response of medaka to an image of a predator fish (donko fish, Odontobutis obscura). The test revealed that the time taken for test medaka exposed to diazepam (0.8, 4, 20, or 100 µg/L) to approach the image was shorter by a factor of 0.22–0.65 and the time spent in the area close to the image was longer by a factor of 1.8–2.7 than in the solvent control group for all diazepam exposure groups (P < 0.05). Hence, we confirmed that the peek‐a‐boo test could detect changes in medaka behavior caused by diazepam with high sensitivity. The peek‐a‐boo test devised in this study is a simple behavioral test with high sensitivity for fish behavioral alteration.

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Duloxetine ameliorates valproicacid‐inducedhyperactivity, anxiety‐like behavior, and social interaction deficits in zebrafish

Cited by 18 publications

References 78 publications

Toxicity and teratogenicity effects of valproic acid on zebrafish (Danio rerio) embryos in relation to autism spectrum disorder

Toxicity and teratogenicity effects of valproic acid on zebrafish (Danio rerio) embryos in relation to autism spectrum disorder

Antagonistic L1 Adhesion Molecule Mimetic Compounds Inhibit Glioblastoma Cell Migration In Vitro

Peek‐A‐Boo Test: A Simple Test for Assessing the Effect of Anxiolytics on Fish Behavior

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