Maternal Transfer of the Cyanobacterial Neurotoxin β-N-Methylamino-L-Alanine (BMAA) via Milk to Suckling Offspring

Abstract

The cyanobacterial neurotoxin β-N-methylamino-L-alanine (BMAA) has been implicated in the etiology of neurodegenerative disease and proposed to be biomagnified in terrestrial and aquatic food chains. We have previously shown that the neonatal period in rats, which in humans corresponds to the last trimester of pregnancy and the first few years of age, is a particularly sensitive period for exposure to BMAA. The present study aimed to examine the secretion of 14C-labeled L- and D-BMAA into milk in lactating mice and the subsequent transfer of BMAA into the developing brain. The results suggest that secretion into milk is an important elimination pathway of BMAA in lactating mothers and an efficient exposure route predominantly for L-BMAA but also for D-BMAA in suckling mice. Following secretion of [14C]L-BMAA into milk, the levels of [14C]L-BMAA in the brains of the suckling neonatal mice significantly exceeded the levels in the maternal brains. In vitro studies using the mouse mammary epithelial HC11 cell line confirmed a more efficient influx and efflux of L-BMAA than of D-BMAA in cells, suggesting enantiomer-selective transport. Competition experiments with other amino acids and a low sodium dependency of the influx suggests that the amino acid transporters LAT1 and LAT2 are involved in the transport of L-BMAA into milk. Given the persistent neurodevelopmental toxicity following injection of L-BMAA to neonatal rodent pups, the current results highlight the need to determine whether BMAA is enriched mother's and cow's milk.

Review and analysis of occurrence, exposure and toxicity of cyanobacteria toxins in food

“…Epidemiological studies, mostly of ecological nature (Caller et al, 2009;Masseret et al, 2013), or cases report studies were also retrieved, investigating possible spatial correlations between a chronic exposure to cyanobacterial neurotoxins including BMAA and development of ALS. These studies arose from the observation that there were clusters of ALS at a higher frequency than expected in areas surrounding lakes, lagoon or other sites periodically affected by cyanobacterial blooms (France; New Hampshire, USA).…”

Intracellular fibril formation, calcification, and enrichment of chaperones, cytoskeletal, and intermediate filament proteins in the adult hippocampus CA1 following neonatal exposure to the nonprotein amino acid BMAA

“…Radiolabelled BMAA is efficiently transferred to mother’s milk in rodents, and the subsequent transfer to the suckling pup results in a high exposure to the neonatal brain (Andersson et al 2013 ). BMAA is a developmental neurotoxicant that can induce a suite of changes (Engskog et al 2013 ; Karlsson et al 2009a , b , 2013a , b ), including long-term learning and memory deficits (Karlsson et al 2009c , 2011 ) as well as regionally restricted neuronal degeneration, necrosis, mineralization, and astrogliosis in the adult rat hippocampus (Karlsson et al 2012 ).…”

Assessment of the mutagenic and genotoxic activity of cyanobacterial toxin beta-N-methyl-amino-L-alanine in Salmonella typhimurium

“…Hence, the presence of L-BMAA in the environment may represent a public health concern. Furthermore, in mice model BMAA can be maternally transferred, either directly (Karlsson et al, 2009a) or trough milk during lactation (Andersson et al, 2013), which means that it is likely that exposure to L-BMAA can have transgenerational effects.…”