Detection of the cyanotoxins L-BMAA uptake and accumulation in primary neurons and astrocytes

Vanessa X. Tan, Claire Mazzocco, Bianca Varney, Dominique Bodet, Tristan A. Guillemin, Alban Bessede, Gilles J. Guillemin

Research output: Contribution to journalArticleResearchpeer-review

Abstract

We show for the first time that a newly developed polyclonal antibody (pAb) can specifically target the cyanotoxin β-methylamino-L-alanine (BMAA) and can be used to enable direct visualization of BMAA entry and accumulation in primary brain cells. We used this pAb to investigate the effect of acute and chronic accumulation, and toxicity of both BMAA and its natural isomer 2,4-diaminobutyric acid (DAB), separately or in combination, on primary cultures of rat neurons. We further present evidence that co-treatment with BMAA and DAB increased neuronal death, as measured by MAP2 fluorescence level, and appeared to reduce BMAA accumulation. DAB is likely to be acting synergistically with BMAA resulting in higher level of cellular toxicity. We also found that glial cells such as microglia and astrocytes are also able to directly uptake BMAA indicating that additional brain cell types are affected by BMAA-induced toxicity. Therefore, BMAA clearly acts at multiple cellular levels to possibly increase the risk of developing neurodegenerative diseases, including neuro- and gliotoxicity and synergetic exacerbation with other cyanotoxins.

LanguageEnglish
Pages55–61
Number of pages7
JournalNeurotoxicity Research
Volume33
Issue number1
DOIs
Publication statusPublished - Jan 2018

Fingerprint

Astrocytes
Neurons
Toxicity
Brain
Neurodegenerative diseases
Antibodies
Microglia
Neuroglia
Isomers
Neurodegenerative Diseases
Rats
Visualization
Fluorescence
2,4-diaminobutyric acid
beta-N-methylamino-L-alanine

Keywords

  • BMAA
  • DAB
  • Glial cells
  • Neurotoxicity

Cite this

Tan, Vanessa X. ; Mazzocco, Claire ; Varney, Bianca ; Bodet, Dominique ; Guillemin, Tristan A. ; Bessede, Alban ; Guillemin, Gilles J. / Detection of the cyanotoxins L-BMAA uptake and accumulation in primary neurons and astrocytes. In: Neurotoxicity Research. 2018 ; Vol. 33, No. 1. pp. 55–61.
@article{9d8d20af469a49288aeab85fd289da1a,
title = "Detection of the cyanotoxins L-BMAA uptake and accumulation in primary neurons and astrocytes",
abstract = "We show for the first time that a newly developed polyclonal antibody (pAb) can specifically target the cyanotoxin β-methylamino-L-alanine (BMAA) and can be used to enable direct visualization of BMAA entry and accumulation in primary brain cells. We used this pAb to investigate the effect of acute and chronic accumulation, and toxicity of both BMAA and its natural isomer 2,4-diaminobutyric acid (DAB), separately or in combination, on primary cultures of rat neurons. We further present evidence that co-treatment with BMAA and DAB increased neuronal death, as measured by MAP2 fluorescence level, and appeared to reduce BMAA accumulation. DAB is likely to be acting synergistically with BMAA resulting in higher level of cellular toxicity. We also found that glial cells such as microglia and astrocytes are also able to directly uptake BMAA indicating that additional brain cell types are affected by BMAA-induced toxicity. Therefore, BMAA clearly acts at multiple cellular levels to possibly increase the risk of developing neurodegenerative diseases, including neuro- and gliotoxicity and synergetic exacerbation with other cyanotoxins.",
keywords = "BMAA, DAB, Glial cells, Neurotoxicity",
author = "Tan, {Vanessa X.} and Claire Mazzocco and Bianca Varney and Dominique Bodet and Guillemin, {Tristan A.} and Alban Bessede and Guillemin, {Gilles J.}",
year = "2018",
month = "1",
doi = "10.1007/s12640-017-9787-9",
language = "English",
volume = "33",
pages = "55–61",
journal = "Neurotoxicity Research",
issn = "1029-8428",
publisher = "Springer, Springer Nature",
number = "1",

}

Detection of the cyanotoxins L-BMAA uptake and accumulation in primary neurons and astrocytes. / Tan, Vanessa X.; Mazzocco, Claire; Varney, Bianca; Bodet, Dominique; Guillemin, Tristan A.; Bessede, Alban; Guillemin, Gilles J.

In: Neurotoxicity Research, Vol. 33, No. 1, 01.2018, p. 55–61.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Detection of the cyanotoxins L-BMAA uptake and accumulation in primary neurons and astrocytes

AU - Tan, Vanessa X.

AU - Mazzocco, Claire

AU - Varney, Bianca

AU - Bodet, Dominique

AU - Guillemin, Tristan A.

AU - Bessede, Alban

AU - Guillemin, Gilles J.

PY - 2018/1

Y1 - 2018/1

N2 - We show for the first time that a newly developed polyclonal antibody (pAb) can specifically target the cyanotoxin β-methylamino-L-alanine (BMAA) and can be used to enable direct visualization of BMAA entry and accumulation in primary brain cells. We used this pAb to investigate the effect of acute and chronic accumulation, and toxicity of both BMAA and its natural isomer 2,4-diaminobutyric acid (DAB), separately or in combination, on primary cultures of rat neurons. We further present evidence that co-treatment with BMAA and DAB increased neuronal death, as measured by MAP2 fluorescence level, and appeared to reduce BMAA accumulation. DAB is likely to be acting synergistically with BMAA resulting in higher level of cellular toxicity. We also found that glial cells such as microglia and astrocytes are also able to directly uptake BMAA indicating that additional brain cell types are affected by BMAA-induced toxicity. Therefore, BMAA clearly acts at multiple cellular levels to possibly increase the risk of developing neurodegenerative diseases, including neuro- and gliotoxicity and synergetic exacerbation with other cyanotoxins.

AB - We show for the first time that a newly developed polyclonal antibody (pAb) can specifically target the cyanotoxin β-methylamino-L-alanine (BMAA) and can be used to enable direct visualization of BMAA entry and accumulation in primary brain cells. We used this pAb to investigate the effect of acute and chronic accumulation, and toxicity of both BMAA and its natural isomer 2,4-diaminobutyric acid (DAB), separately or in combination, on primary cultures of rat neurons. We further present evidence that co-treatment with BMAA and DAB increased neuronal death, as measured by MAP2 fluorescence level, and appeared to reduce BMAA accumulation. DAB is likely to be acting synergistically with BMAA resulting in higher level of cellular toxicity. We also found that glial cells such as microglia and astrocytes are also able to directly uptake BMAA indicating that additional brain cell types are affected by BMAA-induced toxicity. Therefore, BMAA clearly acts at multiple cellular levels to possibly increase the risk of developing neurodegenerative diseases, including neuro- and gliotoxicity and synergetic exacerbation with other cyanotoxins.

KW - BMAA

KW - DAB

KW - Glial cells

KW - Neurotoxicity

UR - http://www.scopus.com/inward/record.url?scp=85028771005&partnerID=8YFLogxK

UR - http://purl.org/au-research/grants/arc/FT120100397

UR - http://purl.org/au-research/grants/arc/DP160105005

U2 - 10.1007/s12640-017-9787-9

DO - 10.1007/s12640-017-9787-9

M3 - Article

VL - 33

SP - 55

EP - 61

JO - Neurotoxicity Research

T2 - Neurotoxicity Research

JF - Neurotoxicity Research

SN - 1029-8428

IS - 1

ER -