دورية أكاديمية
The Cyanotoxin 2,4-DAB Reduces Viability and Causes Behavioral and Molecular Dysfunctions Associated with Neurodegeneration in Larval Zebrafish.
| العنوان: | The Cyanotoxin 2,4-DAB Reduces Viability and Causes Behavioral and Molecular Dysfunctions Associated with Neurodegeneration in Larval Zebrafish. |
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| المؤلفون: | Martin RM; Department of Biological Sciences, North Carolina State University, Raleigh, NC, USA., Bereman MS; Department of Biological Sciences, North Carolina State University, Raleigh, NC, USA., Marsden KC; Department of Biological Sciences, North Carolina State University, Raleigh, NC, USA. kcmarsde@ncsu.edu. |
| المصدر: | Neurotoxicity research [Neurotox Res] 2022 Apr; Vol. 40 (2), pp. 347-364. Date of Electronic Publication: 2022 Jan 14. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Springer Country of Publication: United States NLM ID: 100929017 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1476-3524 (Electronic) Linking ISSN: 10298428 NLM ISO Abbreviation: Neurotox Res Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: <2009-> : New York : Springer Original Publication: [Amsterdam?] : Harwood Academic Publishers, |
| مواضيع طبية MeSH: | Amino Acids, Diamino*/toxicity , Cyanobacteria* , Neurotoxicity Syndromes*, Animals ; Cyanobacteria Toxins ; Isomerism ; Larva ; Neurotoxins/toxicity ; Zebrafish |
| مستخلص: | Exposure to cyanotoxins has been linked to neurodegenerative diseases, including amyotrophic lateral sclerosis, Alzheimer's, and Parkinson's disease. While the cyanotoxin β-methylamino-L-alanine (BMAA) has received much attention, cyanobacteria produce many cyanotoxic compounds, several of which have been detected in nature alongside BMAA, including 2,4-diaminobutyric acid (2,4-DAB) and N-(2-aminoethyl)glycine (AEG). Thus, the question of whether 2,4-DAB and AEG also cause neurotoxic effects in vivo is of great interest, as is the question of whether they interact to enhance toxicity. Here, we evaluate the toxic and neurotoxic effects of these cyanotoxins alone or in combination by measuring zebrafish larval viability and behavior after exposure. 2,4-DAB was the most potent cyanotoxin as it decreased larval viability by approximately 50% at 6 days post fertilization, while BMAA and AEG decreased viability by just 16% and 8%, respectively. Although we only observed minor neurotoxic effects on spontaneous locomotion, BMAA and AEG enhanced acoustic startle sensitivity, and they interacted in an additive manner to exert their effects. 2,4-DAB; however, only modulated startle kinematics, an indication of motor dysfunction. To investigate the mechanisms of 2,4-DAB's effects, we analyzed the protein profile of larval zebrafish exposed to 500 µM 2,4-DAB at two time points and identified molecular signatures consistent with neurodegeneration, including disruption of metabolic pathways and downregulation of the ALS-associated genes SOD1 and UBQLN4. Together, our data demonstrate that BMAA and its isomers AEG and 2,4-DAB cause neurotoxic effects in vivo, with 2,4-DAB as the most potent of the three in the zebrafish model. (© 2022. The Author(s).) |
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| معلومات مُعتمدة: | P30 ES025128 United States ES NIEHS NIH HHS; R01 NS116354 United States NS NINDS NIH HHS; R01NS116354 United States NS NINDS NIH HHS |
| فهرسة مساهمة: | Keywords: 2,4-DAB; Behavior; Cyanotoxins; Mixtures; Proteomics; Zebrafish |
| المشرفين على المادة: | 0 (Amino Acids, Diamino) 0 (Cyanobacteria Toxins) 0 (Neurotoxins) |
| تواريخ الأحداث: | Date Created: 20220114 Date Completed: 20220426 Latest Revision: 20240715 |
| رمز التحديث: | 20240715 |
| مُعرف محوري في PubMed: | PMC9035002 |
| DOI: | 10.1007/s12640-021-00465-4 |
| PMID: | 35029765 |
| قاعدة البيانات: | MEDLINE |
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| DOI: | 10.1007/s12640-021-00465-4 |