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Polyphenol-Rich Cocoa Powder Improve...
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Li, Jeffrey,
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Polyphenol-Rich Cocoa Powder Improves Behavioural Functionality and Gut Morphology in a Zebrafish Model of Autism /
紀錄類型:
書目-電子資源 : Monograph/item
正題名/作者:
Polyphenol-Rich Cocoa Powder Improves Behavioural Functionality and Gut Morphology in a Zebrafish Model of Autism // Jeffrey Li.
作者:
Li, Jeffrey,
面頁冊數:
1 electronic resource (157 pages)
附註:
Source: Masters Abstracts International, Volume: 86-04.
Contained By:
Masters Abstracts International86-04.
標題:
Autism. -
電子資源:
https://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=31527096
ISBN:
9798342118729
Polyphenol-Rich Cocoa Powder Improves Behavioural Functionality and Gut Morphology in a Zebrafish Model of Autism /
Li, Jeffrey,
Polyphenol-Rich Cocoa Powder Improves Behavioural Functionality and Gut Morphology in a Zebrafish Model of Autism /
Jeffrey Li. - 1 electronic resource (157 pages)
Source: Masters Abstracts International, Volume: 86-04.
Valproic acid is an anticonvulsant that has been implicated as risk factor for autism spectrum disorder (ASD) when taken during pregnancy and has been used to induce ASD in animal models. Interventions for ASD predominantly aim at addressing specific comorbid conditions, encompassing therapeutic approaches for anxiety, behavioral issues, communication challenges, as well as occupational and nutritional needs. Although numerous treatments yield efficacy in mitigating the symptoms of ASD and enhancing quality of life, they invariably impose supplementary burdens in terms of financial expenditure and time commitment. This can be difficult to manage for busy families, which is why new treatments that are easy to administer and cheap to acquire are critical. Within this context, cocoa polyphenols have emerged as a compelling candidate for ASD therapy, backed by studies emphasizing their potential cognitive benefits in adults. Further supporting this proposition is a trial conducted with children diagnosed with ASD, which reported notable improvements in behavioral metrics. This thesis describes an evaluation of the efficacy of treating behavioural and physiological symptoms of autism spectrum disorder (ASD), using cocoa powder, in a zebrafish model. Firstly, a valproic acid (VPA) induced model of ASD was validated in zebrafish. VPA toxicology was performed to determine the optimal VPA dosage to induce the autistic phenotype in the zebrafish without causing severe physical damage such as pericardial edemas and swimming disability like ataxia which can obstruct behavioural assessments. Secondly, toxicological assessment of prebiotic cocoa powder, enriched in cocoa polyphenols, was conducted to determine the most favorable exposure concentrations, which would maximize survival rate and dosage, to ensure beneficial modulation of the VPA zebrafish. In terms of the above VPA and cocoa validation studies, the concentrations of compounds were 3 µM and 2.5 µM, respectively. The impact of the treatment in the validated zebrafish ASD model was assessed in terms of behaviour, gut morphology, metabolomics, and proteomics. The VPA-treated zebrafish demonstrated an ASD-like phenotype as they exhibited stressed behaviour with increased and more sporadic swimming patterns. The VPA-treated zebrafish swam larger distances at greater velocities in both dark and light cycles when compared to the control, but also the cocoa and VPA + cocoa groups. Interestingly, the VPA-treated fish with cocoa remained calm and behaved similarly to controls in the dark cycle and remained calmer after transitioning into the light cycle of the assay. VPA treatment caused severe gastrointestinal shrinkage and deformations compared to controls whereas cocoa treatment in the VPA group was associated with gut morphology similar to the control group. VPA-treated zebrafish suffered from displaced and deformed livers compared to all the other groups. Metabolomics revealed significant differences in metabolites present in VPA-treated zebrafish versus the control group. The VPA treatment was associated with increased 5-methoxytryptophan, cystathionine, tryptophan, indoleacrylic acid, D-fructose 1,6-bisphosphate, L-valine, leucine, tyrosine, proline, and 2-octenoyl-carnitine. On the other hand, cocoa treatment of the VPA fish did not exhibit any metabolite differences from controls apart from increased caffeine and theobromine levels. Proteomics revealed significant differences in proteins present in VPA-treated zebrafish versus the control group.
English
ISBN: 9798342118729Subjects--Topical Terms:
526650
Autism.
Polyphenol-Rich Cocoa Powder Improves Behavioural Functionality and Gut Morphology in a Zebrafish Model of Autism /
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Valproic acid is an anticonvulsant that has been implicated as risk factor for autism spectrum disorder (ASD) when taken during pregnancy and has been used to induce ASD in animal models. Interventions for ASD predominantly aim at addressing specific comorbid conditions, encompassing therapeutic approaches for anxiety, behavioral issues, communication challenges, as well as occupational and nutritional needs. Although numerous treatments yield efficacy in mitigating the symptoms of ASD and enhancing quality of life, they invariably impose supplementary burdens in terms of financial expenditure and time commitment. This can be difficult to manage for busy families, which is why new treatments that are easy to administer and cheap to acquire are critical. Within this context, cocoa polyphenols have emerged as a compelling candidate for ASD therapy, backed by studies emphasizing their potential cognitive benefits in adults. Further supporting this proposition is a trial conducted with children diagnosed with ASD, which reported notable improvements in behavioral metrics. This thesis describes an evaluation of the efficacy of treating behavioural and physiological symptoms of autism spectrum disorder (ASD), using cocoa powder, in a zebrafish model. Firstly, a valproic acid (VPA) induced model of ASD was validated in zebrafish. VPA toxicology was performed to determine the optimal VPA dosage to induce the autistic phenotype in the zebrafish without causing severe physical damage such as pericardial edemas and swimming disability like ataxia which can obstruct behavioural assessments. Secondly, toxicological assessment of prebiotic cocoa powder, enriched in cocoa polyphenols, was conducted to determine the most favorable exposure concentrations, which would maximize survival rate and dosage, to ensure beneficial modulation of the VPA zebrafish. In terms of the above VPA and cocoa validation studies, the concentrations of compounds were 3 µM and 2.5 µM, respectively. The impact of the treatment in the validated zebrafish ASD model was assessed in terms of behaviour, gut morphology, metabolomics, and proteomics. The VPA-treated zebrafish demonstrated an ASD-like phenotype as they exhibited stressed behaviour with increased and more sporadic swimming patterns. The VPA-treated zebrafish swam larger distances at greater velocities in both dark and light cycles when compared to the control, but also the cocoa and VPA + cocoa groups. Interestingly, the VPA-treated fish with cocoa remained calm and behaved similarly to controls in the dark cycle and remained calmer after transitioning into the light cycle of the assay. VPA treatment caused severe gastrointestinal shrinkage and deformations compared to controls whereas cocoa treatment in the VPA group was associated with gut morphology similar to the control group. VPA-treated zebrafish suffered from displaced and deformed livers compared to all the other groups. Metabolomics revealed significant differences in metabolites present in VPA-treated zebrafish versus the control group. The VPA treatment was associated with increased 5-methoxytryptophan, cystathionine, tryptophan, indoleacrylic acid, D-fructose 1,6-bisphosphate, L-valine, leucine, tyrosine, proline, and 2-octenoyl-carnitine. On the other hand, cocoa treatment of the VPA fish did not exhibit any metabolite differences from controls apart from increased caffeine and theobromine levels. Proteomics revealed significant differences in proteins present in VPA-treated zebrafish versus the control group.
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L'acide valproique est un antiepileptique qui a ete identifie comme un facteur de risque pour le trouble du spectre de l'autisme (TSA) lorsqu'il est pris pendant la grossesse. Il a aussi ete utilise pour induire le TSA dans des modeles animaux. Les interventions pour le TSA visent principalement a traiter des conditions comorbides specifiques, incluant des approches therapeutiques pour l'anxiete, les problemes de comportement, les defis de communication, ainsi que les besoins occupationnels et nutritionnels. Bien que de nombreux traitements soient efficaces pour attenuer les symptomes du TSA et ameliorer la qualite de vie, ils imposent invariablement des fardeaux supplementaires en termes de depenses financieres et de temps d'administration. Cela peut etre difficile a gerer pour les familles occupees, c'est pourquoi de nouveaux traitements faciles a administrer et pas chers a acquerir sont essentiels. Dans ce contexte, les polyphenols de cacao sont un candidat prometteur pour la therapie du TSA, soutenus par des etudes qui soulignent leurs avantages cognitifs potentiels chez les adultes. Une etude menee aupres d'enfants diagnostiques avec des TSA a rapporte des ameliorations notables dans les analyses comportementales. De plus, en tant que complement nutritionnel, la poudre de cacao est egalement un prebiotique qui peut ameliorer la sante gastro-intestinale, ce qui est important dans le TSA puisque la dysbiose intestinale et la dyspepsie sont des comorbidites courantes. Cette these decrit une evaluation de l'efficacite du traitement des symptomes comportementaux et physiologiques du trouble du spectre de l'autisme (TSA), en utilisant la poudre de cacao, dans un modele de poisson-zebre. D'abord, un modele de TSA induit par l'acide valproique (VPA) a ete valide chez le poisson-zebre. La toxicologie du VPA a ete realisee pour determiner la dose optimale de VPA pour induire le phenotype autistique chez le poisson-zebre sans causer de handicap physique severe. Ensuite, une toxicologie de la poudre de cacao prebiotique a ete menee pour determiner les concentrations d'exposition les plus favorables pour assurer des effets benefiques sur le poisson-zebre traite de VPA. En ce qui concerne les etudes sur le VPA et le cacao, les concentrations ideales des composes etaient quasiment similaires, respectivement de 3 µM et 2,5 µM. L'impact du traitement par le cacao dans le modele de TSA de poisson-zebre a ete evalue en termes de comportement, de morphologie intestinale, de metabolomique et de proteomique. Les poissons-zebres traites au VPA ont demontre un phenotype semblable au TSA car ils ont presente un comportement stresse avec des motifs de nage accrus et plus sporadiques. Les poissons-zebres traites au VPA ont nage de plus grandes distances a des vitesses plus elevees dans les cycles sombres et lumineux par rapport au controle, mais aussi par rapport aux groupes cacao et VPA + cacao. Les poissons traites au VPA avec du cacao sont restes calmes et se sont comportes de maniere similaire aux controles dans le cycle sombre et sont restes plus calmes apres la transition vers le cycle lumineux de l'experience. Le traitement au VPA a cause une reduction severe et des deformations du tractus gastro-intestinal par rapport aux controles alors que le traitement au cacao dans le groupe VPA a ete associe a une morphologie intestinale similaire a celle du groupe de controle.
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