Screening selected medicinal plants for potential anxiolytic activity using an in vivo zebrafish model

Maphanga, Veronica B.; Skalicka-Woźniak, Krystyna; Budzyńska, Barbara; Enslin, Gill; Viljoen, Alvaro

doi:10.1007/s00213-020-05642-5

Cited by 11 publications

(11 citation statements)

References 58 publications

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“…Many aspects of development examined in the necab2 mutant so far appeared normal: the grossly normal appearance ( Figure 4A ), normal neural development and cytoarchitecture ( Figure 4B ), and the balanced composition of neuronal subtypes ( Figure 4C ), as well as good fertility in adulthood (data not shown). To determine whether the necab2 mutant displayed altered behaviors as those commonly observed in ASD patients, we recorded larval locomotion and anxiety-associated behaviors, adapted as markers of ASD behaviors in zebrafish ( Kozol et al, 2015 ; Zimmermann et al, 2015 ; Li et al, 2019 ; Maphanga et al, 2020 ). To control for possible differences in genetic backgrounds, behavioral tracking was performed on the progeny derived from heterozygous necab2 +/– mating, followed by blind genotyping ( Figure 5A ).…”

Section: Resultsmentioning

confidence: 99%

Autism-Risk Gene necab2 Regulates Psychomotor and Social Behavior as a Neuronal Modulator of mGluR1 Signaling

Chen

Long

Guo

et al. 2022

Front. Mol. Neurosci.

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BackgroundDe novo deletion of the neuronal calcium-binding protein 2 (NECAB2) locus is associated with idiopathic autism spectrum disorders (ASDs). The in vivo function of NECAB2 in the brain remains largely elusive.MethodsWe investigated the morphological and behavioral profiles of both necab2 knock-out and overexpression zebrafish models. The expression pattern and molecular role of necab2 were probed through a combination of in vitro and in vivo assays.ResultsWe show that Necab2 is a neuronal specific, cytoplasmic, and membrane-associated protein, abundantly expressed in the telencephalon, habenula, and cerebellum. Necab2 is distributed peri-synaptically in subsets of glutamatergic and GABAergic neurons. CRISPR/Cas9-generated necab2 knock-out zebrafish display normal morphology but exhibit a decrease in locomotor activity and thigmotaxis with impaired social interaction only in males. Conversely, necab2 overexpression yields behavioral phenotypes opposite to the loss-of-function. Proteomic profiling uncovers a role of Necab2 in modulating signal transduction of G-protein coupled receptors. Specifically, co-immunoprecipitation, immunofluorescence, and confocal live-cell imaging suggest a complex containing NECAB2 and the metabotropic glutamate receptor 1 (mGluR1). In vivo measurement of phosphatidylinositol 4,5-bisphosphate further substantiates that Necab2 promotes mGluR1 signaling.ConclusionsNecab2 regulates psychomotor and social behavior via modulating a signaling cascade downstream of mGluR1.

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Section: Resultsmentioning

confidence: 99%

Autism-Risk Gene necab2 Regulates Psychomotor and Social Behavior as a Neuronal Modulator of mGluR1 Signaling

Chen

Long

Guo

et al. 2022

Front. Mol. Neurosci.

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“…Increased locomotor activity is one of the behaviors that characterize anxiety in human (Maphanga et al, 2020). nde1 deficiency results in increasement in locomotor activity that does not habituate over time.…”

Section: Discussionmentioning

confidence: 99%

Deficiency of nde1 in zebrafish induces brain inflammatory responses and autism-like behavior

Zhang

Lin

et al. 2022

iScience

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“…As would be seen in this review, in adult zebrafish the novel tank and light/dark chamber are the most widely used models of anxiety (Kysil et al, 2017 ) and have been extensively validated, even as a test battery (Fontana et al, 2021 ). On the other hand, light-dark transitions are a common anxiety protocol for larvae zebrafish (Peng et al, 2016 ), which has also been successfully used to screen medicinal plants for potential anxiolytic effects (Maphanga et al, 2020 ).…”

Section: Anxiety Models In Adult Zebrafishmentioning

confidence: 99%

“…In this sense, zebrafish larvae have been widely used in first for toxicity assessment of crude extracts from plants, specific secondary metabolites or Traditional Chinese medicine (Chahardehi et al, 2020 ; Zhang et al, 2022 ) due to the easy exposure to drug and testing that allows high-throughput toxicity screening, the short times of development and low costs. More recently, behavioral protocols with larvae zebrafish using the light-dark transitions have been proposed to explore new drugs from herbal medicine with potential anxiolytic effects (Muniandy, 2018 ; Maphanga et al, 2020 ).…”

Section: Pharmacological Research On Plant Secondary Metabolites In Z...mentioning

confidence: 99%

Zebrafish as a Useful Tool in the Research of Natural Products With Potential Anxiolytic Effects

Cueto‐Escobedo

Germán-Ponciano

Guillén-Ruiz

et al. 2022

Front. Behav. Neurosci.

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Zebrafish (Danio rerio) is a popular and valuable species used in many different biomedical research areas. The complex behavior that fish exhibit in response to different stimuli allows researchers to explore the biological and pharmacological basis of affective and mood disorders. In this sense, anxiety is commonly studied in preclinical research with animal models in rodents. During the last decade, those models have been successfully adapted to zebrafish. Stressful stimuli, such as novel environments, chemical substances, light conditions, and predator images, can trigger defensive behaviors considered indicators of an anxiety-like state. In the first stage, models were adapted and validated with different stressors and anxiolytic drugs with promising results and are now successfully used to generate scientific knowledge. In that sense, zebrafish allows several routes of administration and other methodological advantages to explore the anxiolytic effects of natural products in behavioral tests as novel tank, light-dark chamber, and black/white maze, among others. The present work will review the main findings on preclinical research using adult zebrafish to explore anxiolytics effects of natural products as plant secondary metabolites such as flavonoids, alkaloids and terpenes or standardized extracts of plants, among others. Scientific literature confirms the utility of zebrafish tests to explore anxiety-like states and anxiolytic-like effects of plant secondary metabolites, which represent a useful and ethical tool in the first stages of behavioral.

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Screening selected medicinal plants for potential anxiolytic activity using an in vivo zebrafish model

Cited by 11 publications

References 58 publications

Autism-Risk Gene necab2 Regulates Psychomotor and Social Behavior as a Neuronal Modulator of mGluR1 Signaling

Autism-Risk Gene necab2 Regulates Psychomotor and Social Behavior as a Neuronal Modulator of mGluR1 Signaling

Deficiency of nde1 in zebrafish induces brain inflammatory responses and autism-like behavior

Zebrafish as a Useful Tool in the Research of Natural Products With Potential Anxiolytic Effects

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