Evaluating amino acids as protectants against β-N-methylamino-l-alanine-induced developmental neurotoxicity in a rat model
| Autor: | Laura Louise Scott, Rianita van Onselen, T.G. Downing |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Rat model Dietary excess Pharmacology Toxicology Rats Sprague-Dawley 03 medical and health sciences 0302 clinical medicine Central Nervous System Diseases Pregnancy medicine Animals Amino Acids Maze Learning chemistry.chemical_classification Developmental neurotoxicity Alanine Behavior Animal Cyanobacteria Toxins Neurodegeneration Neurotoxicity Amino Acids Diamino medicine.disease Rats Amino acid 030104 developmental biology chemistry Prenatal Exposure Delayed Effects 030220 oncology & carcinogenesis Toxicity Female |
| Zdroj: | Toxicology and Applied Pharmacology. 403:115140 |
| ISSN: | 0041-008X |
| Popis: | With accumulating evidence that supports the role of β-N-methylamino-l-alanine (BMAA) in neurodegeneration, it is necessary to elucidate the mechanisms and modes of BMAA toxicity so as to facilitate the search for potential preventative/therapeutic strategies. Daily supplementation with l-serine was suggested as a possible therapy to treat BMAA-induced neurotoxicity, based on the hypothesized mechanism of BMAA misincorporation into proteins for l-serine. As an alternative to misincorporation, it was hypothesized that BMAA toxicity may, in part, be due to its high affinity for associating with hydroxyl group-containing amino acids, and that a dietary excess of the hydroxyl-containing l-serine might offer protection by binding to BMAA and reducing its toxicity. Additionally, l-serine can also reduce the uptake of BMAA into human cells by competitive uptake at ASCT2, and l-phenylalanine, by competitive uptake at LAT1, and l-alanine, by competitive uptake at SNAT2, can also reduce BMAA uptake into human cells. The aim of this study was therefore to determine the protective value of l-serine, l-phenylalanine and l-alanine in reducing the effects of neonatal exposure to BMAA in a Sprague Dawley rat model. Pre-treatment with l-phenylalanine reduced the observed behavioral abnormalities and neuropathologies by 60-70% in most cases. l-serine was also effective in reducing some of the behavioral abnormalities and neuropathologies, most markedly spinal cord neuronal loss. However, the protective effect of l-serine was obfuscated by neuropathies that were observed in l-serine-treated control male rats. l-alanine had no effect in protecting against BMAA-induced neurotoxicity, suggesting that competitive amino acid uptake plays a minor role in protecting against BMAA-induced neurotoxicity. |
| Databáze: | OpenAIRE |
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