Neurotoxicity Research

, Volume 33, Issue 1, pp 87–112 | Cite as

Perinatal Exposure to the Cyanotoxin β-N-Méthylamino-l-Alanine (BMAA) Results in Long-Lasting Behavioral Changes in Offspring—Potential Involvement of DNA Damage and Oxidative Stress

  • Anthony Laugeray
  • Asma Oummadi
  • Clément Jourdain
  • Justyne Feat
  • Géraldine Meyer-Dilhet
  • Arnaud Menuet
  • Karen Plé
  • Marion Gay
  • Sylvain Routier
  • Stéphane Mortaud
  • Gilles J. Guillemin


We recently demonstrated that perinatal exposure to the glutamate-related herbicide, glufosinate ammonium, has deleterious effects on neural stem cell (NSC) homeostasis within the sub-ventricular zone (SVZ), probably leading to ASD-like symptoms in offspring later in life. In the present study, we aimed to investigate whether perinatal exposure to another glutamate-related toxicant, the cyanobacterial amino acid β-N-methylamino-l-alanine (BMAA), might also trigger neurodevelopmental disturbances. With this aim, female mice were intranasally exposed to low doses of BMAA, 50 mg kg−1 three times a week from embryonic days 7–10 to postnatal day 21. Behavioral analyses were performed during the offspring’s early life and during adulthood. Developmental analyses revealed that perinatal exposure to BMAA hastened the appearance of some reflexes and communicative skills. BMAA-exposed offspring displayed sex-dependent changes in emotional cognition shortly after exposure. Later in life, the female offspring continued to express emotional defects and to display abnormal sociability, while males were less affected. To assess whether early exposure to BMAA had deleterious effects on NSC homeostasis, we exposed mice NSCs to 1 and 3 mM BMAA during 24 h. We found that BMAA-exposed NSCs produced high levels of ROS, highlighting the ability of BMAA to induce oxidative stress. We also showed that BMAA exposure increased the number of γH2AX/53BP1 foci per nucleus, suggesting that BMAA-induced DNA damage in NSCs. Collectively, this data strongly suggests that perinatal exposure to the cyanobacteria BMAA, even at low doses, results in neurobehavioral disturbances during both the postnatal period and adulthood. This is considered to be underpinned at the cellular level through dysregulation of NSC homeostasis in the developing brain.


l-β-N-Methylamino-l-alanine (l-BMAA) Cyanotoxin Developmental neurotoxicity Perinatal exposure Mice 



This work was supported by the Australian Research Council (ARC grant number DP160105005 “Biomagnification of the biotoxin BMAA in the environment.”

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© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  1. 1.Experimental and Molecular Immunology and Neurogenetics (INEM), UMR 7355Centre National de la Recherche ScientifiqueOrléansFrance
  2. 2.University of OrléansOrléansFrance
  3. 3.Institute de Chimie Organique et Analytique, UMR 7311Center National de la Recherche ScientifiqueOrléansFrance
  4. 4.Neuroinflammation Group, MND and Neurodegenerative Diseases Research CenterMacquarie UniversitySydneyAustralia

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