title: 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 (14)C-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 [(14)C]L-BMAA into milk, the levels of [(14)C]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.
authors.affiliation: Department of Environmental Toxicology, Uppsala University, Uppsala, Sweden.
authors.forename: Marie
authors.initials: M
authors.lastname: Andersson
authors.forename: Oskar
authors.initials: O
authors.lastname: Karlsson
authors.forename: Ulrika
authors.initials: U
authors.lastname: Bergström
authors.forename: Eva B
authors.initials: EB
authors.lastname: Brittebo
authors.forename: Ingvar
authors.initials: I
authors.lastname: Brandt
mesh_terms: D027182:Amino Acid Transport System y+ / Q000378:metabolism; D027241:Amino Acid Transport System y+L; D000599:Amino Acids, Diamino / Q000032:analysis / Q000378:metabolism*; D000818:Animals; D000833:Animals, Suckling; D001345:Autoradiography; D001427:Bacterial Toxins / Q000032:analysis / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D002250:Carbon Radioisotopes / Q000378:metabolism; D002460:Cell Line; D000087522:Cyanobacteria Toxins; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D027301:Fusion Regulatory Protein 1, Light Chains / Q000378:metabolism; D008387:Marine Toxins / Q000032:analysis / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D052998:Microcystins / Q000032:analysis / Q000378:metabolism*; D008892:Milk / Q000737:chemistry*; D011247:Pregnancy; D018709:Statistics, Nonparametric; D013696:Temperature; D013997:Time Factors
chemical_list: D027182:Amino Acid Transport System y+; D027241:Amino Acid Transport System y+L; D000599:Amino Acids, Diamino; D001427:Bacterial Toxins; D002250:Carbon Radioisotopes; D000087522:Cyanobacteria Toxins; D027301:Fusion Regulatory Protein 1, Light Chains; D008387:Marine Toxins; D052998:Microcystins; C518286:SLC7A8 protein, mouse; C518287:Slc7a7 protein, mouse; C001824:beta-N-methylamino-L-alanine