Neurotoxicity of the cyanotoxin BMAA through axonal degeneration and intercellular spreading

Vanessa X. Tan, Benjamin Lassus, Chai K. Lim, Philippe Tixador, Josquin Courte, Alban Bessede, Gilles J. Guillemin, Jean Michel Peyrin

Research output: Contribution to journalArticleResearchpeer-review

Abstract

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.

LanguageEnglish
Pages62-75
Number of pages14
JournalNeurotoxicity Research
Volume33
Issue number1
DOIs
Publication statusPublished - Jan 2018

Fingerprint

Neurons
Corpus Striatum
Toxicity
Neurodegenerative diseases
Microfluidics
Amyotrophic Lateral Sclerosis
Carisoprodol
Dendrites
Neurodegenerative Diseases
Axons
Antibodies
beta-N-methylamino-L-alanine

Keywords

  • Axonal degeneration
  • BMAA
  • Microfluidics
  • Neurotoxic
  • Spread

Cite this

Tan, Vanessa X. ; Lassus, Benjamin ; Lim, Chai K. ; Tixador, Philippe ; Courte, Josquin ; Bessede, Alban ; Guillemin, Gilles J. ; Peyrin, Jean Michel. / Neurotoxicity of the cyanotoxin BMAA through axonal degeneration and intercellular spreading. In: Neurotoxicity Research. 2018 ; Vol. 33, No. 1. pp. 62-75.
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Neurotoxicity of the cyanotoxin BMAA through axonal degeneration and intercellular spreading. / Tan, Vanessa X.; Lassus, Benjamin; Lim, Chai K.; Tixador, Philippe; Courte, Josquin; Bessede, Alban; Guillemin, Gilles J.; Peyrin, Jean Michel.

In: Neurotoxicity Research, Vol. 33, No. 1, 01.2018, p. 62-75.

Research output: Contribution to journalArticleResearchpeer-review

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