Cerebral uptake and protein incorporation of cyanobacterial toxin β-N-methylamino-L-alanine

Xiaobin Xie, Margaret Basile, Deborah C Mash

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)779-784
Number of pages6
JournalNeuroReport
Volume24
Issue number14
DOIs
StatePublished - Sep 13 2013

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Alanine
Brain
Proteins
Amyotrophic Lateral Sclerosis
Amino Acids
Trichloroacetic Acid
Choroid Plexus
cyanobacterial toxin
Poisons
Parkinsonian Disorders
Cyanobacteria
Brain Diseases
Protein C
Autoradiography
Intravenous Administration
Radioactivity
Half-Life
Dementia
beta-N-methylamino-L-alanine
Alzheimer Disease

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

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 journalArticle

Xie, Xiaobin ; Basile, Margaret ; Mash, Deborah C. / Cerebral uptake and protein incorporation of cyanobacterial toxin β-N-methylamino-L-alanine. In: NeuroReport. 2013 ; Vol. 24, No. 14. pp. 779-784.
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