β-N-methylamino-L-alanine (BMAA) is a nonprotein amino acid produced by diverse species of free-living cyanobacteria found in terrestrial and aquatic environments worldwide. BMAA has been detected as a soluble (free) and insoluble protein-bound (bound) amino acid in brains of Alzheimer's disease, amyotrophic lateral sclerosis, and Guamanian amyotrophic lateral sclerosis/Parkinsonism dementia complex patients. A toxic reservoir of BMAA in the brain may be excitotoxic to neurons or serve to disrupt cerebral protein homeostasis. Here, we report tracer uptake kinetics and a time course for protein incorporation of [C]-L-BMAA into the brain of C57/BL6 mice. BMAA pharmacokinetic parameters measured in plasma show a rapid distribution phase and a terminal elimination half-life of 1.7 days following bolus intravenous administration. Total [C]-L-BMAA uptake to the brain reached a maximum at 1.5 h. Ex-vivo autoradiography of [C]-labeled BMAA showed dense labeling within the ventricles, choroid plexus, and whole-brain gray matter structures. Radioactivity measured in soluble and trichloroacetic acid precipitates was compared to determine the incorporation of [C]-L-BMAA into total brain protein. The maximal concentration of [C]-L-BMAA was measured in protein-bound fractions of brain at 4 h, followed by a corresponding decrease in the free pool of this nonprotein amino acid. The time-dependent association of [C]-L-BMAA in the protein-bound fraction suggests that BMAA may be trapped in new proteins by protein synthesis-dependent processes. BMAA may accumulate into growing polypeptide chains and recycle to the free pool with protein turnover.
ASJC Scopus subject areas
Cerebral uptake and protein incorporation of cyanobacterial toxin β-N-methylamino-L-alanine. / Xie, Xiaobin; Basile, Margaret; Mash, Deborah C.In: NeuroReport, Vol. 24, No. 14, 13.09.2013, p. 779-784.
Research output: Contribution to journal › Article
TY - JOUR
T1 - Cerebral uptake and protein incorporation of cyanobacterial toxin β-N-methylamino-L-alanine
AU - Xie, Xiaobin
AU - Basile, Margaret
AU - Mash, Deborah C
PY - 2013/9/13
Y1 - 2013/9/13
N2 - Lippincott Williams and Wilkins.
AB - Lippincott Williams and Wilkins.
UR - http://www.scopus.com/inward/record.url?scp=84883642614&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84883642614&partnerID=8YFLogxK
U2 - 10.1097/WNR.0b013e328363fd89
DO - 10.1097/WNR.0b013e328363fd89
M3 - Article
C2 - 23979257
AN - SCOPUS:84883642614
VL - 24
SP - 779
EP - 784
JO - NeuroReport
JF - NeuroReport
SN - 0959-4965
IS - 14