2-Amino-3-(methylamino)propanoic acid (BMAA) bioavailability in the primate

Metabotropic Glutamate Receptor 1 Mediates the Electrophysiological and Toxic Actions of the Cycad Derivative β-N-Methylamino-l-Alanine on Substantia Nigra Pars Compacta DAergic Neurons

“…For this reason, only recent studies properly quantified the concentration of BMAA in postmortem brain tissues of patients (Murch et al, 2004;Pablo et al, 2009), using validated methods able to detect either the free or the protein-bound BMAA portions. Taking into account the findings by Duncan et al (1991), reporting that 10 -30 g/g BMAA in the rat brain corresponds approximately to the concentration of Յ0.25 mM, it can be concluded that BMAA concentration in the human brain of patients is in the low millimolar range. The deleterious mechanisms of the toxin could underlie neurological conditions such as ALS-PDC and, potentially, idiopathic Parkinson's disease.…”

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

“…However, concerning the kinetics of its uptake and metabolism, a reasonable number of papers was retrieved and examined. Oral bioavailability, biodistribution and brain uptake of BMAA was early demonstrated by Duncan et al (1991) after intravenous and oral administration in rats (1991) and primates (1992). The mechanism of BMAA uptake into brain was demonstrated by Smith et al (1992) in rats using an in situ brain perfusion technique, showing that BMAA influx was found to be saturable with a maximal transfer rate (Vmax) of 1.6 ± 0.3 × 10 -3 μmol/s/g and a half-saturation constant (Km) of 2.9 ± 0.7 mM.…”

Analysis, occurrence, and toxicity of ß-methylaminoalanine (BMAA)

“…It is notable that Duncan et al (1991) states that the influx of BMAA into the rat brain is comparable to that of tracers used as markers of passive permeability through the blood-brain barrier, and 10-100 times lower than amino acids transported by the large neutral amino acid carrier. Smith et al (1992), on the other hand, concludes from studies using an in situ brain perfusion technique that BMAA is taken up into the brain by the large neutral amino acid carrier and may be sensitive to the same factors that affect neutral amino acid transport, such as diet, disease and age.…”

“…The authors note that in previous experiments with the same battery of behavioural tests and histological protocols, mice fed cycads that contained no BMAA or MAM showed motor and cognitive deficits, as well as decreased neuronal numbers and signs of apoptosis in the ventral spinal cord and other CNS areas . It was also noted that pharmacokinetic studies by Duncan et al (1991) had shown that BMAA reaches potentially toxic levels in the CNS when administered at dose levels that are orders of magnitude higher than environmentally available levels and that BMAA is a very weak glutamate agonist that gives rise to damage at levels in the millimolar range, whereas most excitotoxins are active in the micromolar range. Overall, the findings in this study did not support a causal role for BMAA in ALS-PDC or other neurodegenerative disease, according to the authors (Cruz-Aguado et al, 2006) 4.5 Studies on infusion of BMAA directly into brain or brain ventricles Intracerebroventricular (i.c.v.…”

“…Duncan and co-workers theoretically asessed the significance of this route of administration, focusing on the levels of BMAA that can be reached in the circulation. Based on a known BMAA content in cycad seeds and assuming a daily use of freshly prepared poultice for one month, Duncan et al (1991) calculated the worst-case daily dose to be 0.36 mg/kg bodyweight and the accumulated dose to be 10.8 mg/kg/month. .…”