Perinatal Exposure to the Cyanotoxin ß-N-Méthylamino-L-Alanine (BMAA) Results in Long-Lasting Behavioral Changes in Offspring-Potential Involvement of DNA Damage and Oxidative Stress.
Neurotox Res
; 33(1): 87-112, 2018 Jan.
Article
em En
| MEDLINE
| ID: mdl-28879461
ABSTRACT
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 ß-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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Efeitos Tardios da Exposição Pré-Natal
/
Dano ao DNA
/
Estresse Oxidativo
/
Diamino Aminoácidos
/
Transtornos Mentais
/
Neurotoxinas
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
Limite:
Animals
/
Pregnancy
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article