Transfer of developmental neurotoxin β-N-methylamino-l-alanine (BMAA) via milk to nursed offspring: Studies by mass spectrometry and image analysis.
The cyanobacterial non-proteinogenic amino acid β-N-methylamino-l-alanine (BMAA) is proposed to be involved in the etiology of amyotrophic lateral sclerosis/parkinsonism dementia complex. When administered as single doses to neonatal rats, BMAA gives rise to cognitive and neurodegenerative impairments in the adult animal. Here, we employed mass spectrometry (LC-MS/MS) and autoradiographic imaging to examine the mother-to-pup transfer of BMAA in rats. The results show that unchanged BMAA was secreted into the milk and distributed to the suckling pups. The concentration of BMAA in pup stomach milk and the neonatal liver peaked after 8h, while the concentration in the pup brain increased throughout the study period. About 1 and 6% of the BMAA recovered from adult liver and brain were released following hydrolysis, suggesting that this fraction was associated with protein. No association to milk protein was observed. Injection of rat pups with [methyl-(14)C]-l-BMAA or [carboxyl-(14)C]-l-BMAA resulted in highly similar distribution patterns, indicating no or low metabolic elimination of the methylamino- or carboxyl groups. In conclusion, BMAA is transported as a free amino acid to rat milk and suckling pups. The results strengthen the proposal that mothers' milk could be a source of exposure for BMAA in human infants.
Department of Environmental Toxicology, Uppsala University, SE-752 36 Uppsala, Sweden.
Marie
M
Andersson
Department of Pharmaceutical Biosciences, Uppsala University, SE-751 24 Uppsala, Sweden; Department of Clinical Neuroscience, Karolinska Institutet, Center for Molecular Medicine, SE-17176 Stockholm, Sweden.
Oskar
O
Karlsson
Institute for Ethnomedicine, PO Box 3464, Jackson, WY 83001, USA.
Sandra Anne
SA
Banack
Department of Environmental Toxicology, Uppsala University, SE-752 36 Uppsala, Sweden. Electronic address: Ingvar.Brandt@ebc.uu.se.
Ingvar
I
Brandt
D000599:Amino Acids, Diamino / Q000032:analysis / Q000378:metabolism / Q000633:toxicity*; D000818:Animals; D000831:Animals, Newborn; D001345:Autoradiography; D001427:Bacterial Toxins / Q000032:analysis / Q000378:metabolism / Q000633:toxicity*; D001921:Brain / Q000254:growth & development / Q000378:metabolism; D002250:Carbon Radioisotopes; D002851:Chromatography, High Pressure Liquid; D000087522:Cyanobacteria Toxins; D018690:Excitatory Amino Acid Agonists / Q000032:analysis / Q000378:metabolism / Q000633:toxicity*; D005260:Female; D007774:Lactation; D008099:Liver / Q000254:growth & development / Q000378:metabolism; D018811:Maternal Exposure / Q000009:adverse effects*; D008892:Milk / Q000737:chemistry / Q000378:metabolism; D011247:Pregnancy; D017208:Rats, Wistar; D021241:Spectrometry, Mass, Electrospray Ionization; D053719:Tandem Mass Spectrometry; D014018:Tissue Distribution; D066007:Toxicokinetics
D000599:Amino Acids, Diamino; D001427:Bacterial Toxins; D002250:Carbon Radioisotopes; D000087522:Cyanobacteria Toxins; D018690:Excitatory Amino Acid Agonists; C001824:beta-N-methylamino-L-alanine
BMAA; Cyanobacterial neurotoxin,kinetics; Developmental neurotoxicity; Milk secretion; Mother-to-offspring transfer