Neurotoxicity of the Cyanotoxin BMAA Through Axonal Degeneration and Intercellular Spreading
| Autor: | Josquin Courte, Alban Bessede, Benjamin Lassus, Chai K. Lim, Vanessa Tan, Philippe Tixador, Jean-Michel Peyrin, Gilles J. Guillemin |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Somatic cell Neurotoxins Biology Toxicology Mice 03 medical and health sciences 0302 clinical medicine Tubulin Lab-On-A-Chip Devices Glial Fibrillary Acidic Protein medicine Animals Amyotrophic lateral sclerosis Transcellular Cells Cultured Neurons Analysis of Variance Cyanobacteria Toxins Dose-Response Relationship Drug General Neuroscience Neurodegeneration Neurotoxicity Amino Acids Diamino Brain Cyanotoxin Embryo Mammalian medicine.disease Axons 030104 developmental biology nervous system Nerve Degeneration Toxicity Nerve Net Transcytosis Microtubule-Associated Proteins Neuroscience 030217 neurology & neurosurgery Intracellular |
| Zdroj: | Neurotoxicity Research. 33:62-75 |
| ISSN: | 1476-3524 1029-8428 |
| Popis: | β-Methylamino-L-alanine (BMAA) is implicated in neurodegeneration and neurotoxicity, particularly in ALS-Parkinson Dementia Complex. Neurotoxic properties of BMAA have been partly elucidated, while its transcellular spreading capacity has not been examined. Using reconstructed neuronal networks in microfluidic chips, separating neuronal cells into two subcompartments-(1) the proximal, containing first-order neuronal soma and dendrites, and (2) a distal compartment, containing either only axons originating from first-order neurons or second-order striatal neurons-creates a cortico-striatal network. Using this system, we investigated the toxicity and spreading of BMAA in murine primary neurons. We used a newly developed antibody to detect BMAA in cells. After treatment with 10 μM BMAA, the cyanotoxin was incorporated in first-degree neurons. We also observed a rapid trans-neuronal spread of BMAA to unexposed second-degree neurons in 48 h, followed by axonal degeneration, with limited somatic death. This in vitro study demonstrates BMAA axonal toxicity at sublethal concentrations and, for the first time, the transcellular spreading abilities of BMAA. This neuronal dying forward spread that could possibly be associated with progression of some neurodegenerative diseases especially amyotrophic lateral sclerosis. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink