Introduction
The neurotoxin β-N -methylamino-L -alanine (BMAA)
(Supplementary Fig. 1) was hypothesized as an environmental factor
responsible to the endemic amyotrophic lateral sclerosis-parkinsonism
dementia complex (ALS-PDC) in Guam and other globally sporadic
neurodegenerative diseases including ALS and Alzheimer’s disease
(AD)1-4. Symbiotic cyanobacteria in the coralloid
roots of cycad trees were demonstrated as the producer of BMAA in
Guam5, which was followed by several studies showing
positive detection of BMAA in diverse free-living cyanobacteria in
seawater or freshwater environments6-14. Later some
eukaryotic organisms such as dinoflagellates15,16 and
diatoms17-19 were reported to produce this neurotoxin.
Significant bioaccumulation and biomagnification of BMAA were reported
in zooplankton and various vertebrates (fish) and invertebrates
(mussels, oysters) in Baltic Sea dominated by massive surface
cyanobacterial blooms20, following the report on BMAA
biomagnification in the Guam ecosystem5. Varied
concentrations of BMAA (nd to ~7000 µg
g-1) were detected in diverse resident animals
suffering from cyanobacterial blooms in the South Florida aquatic
ecosystem6. Six freshwater aquaculture products in
different trophic levels also contained BMAA in the Taihu Lake Basin
with chronic pollution of cyanobacterial blooms21. The
feeding patterns (plankton-benthivorous) and increased age of fish
leading to a higher concentration of BMAA was also found in the Lake
Finjasjön in southern Sweden22. Muscle, liver, and
brain tissue samples of a huge carp from the Lake Mascoma, as well as
filtered aerosol samples contained BMAA23.
Additionally, positive detection of BMAA was reported in mussels and
other mollusks in French coasts24-26, in
Sweden27,28, as well as in diverse filter-feeding
mollusks or benthic gastropod in China29,30.
Expectedly higher concentrations of BMAA [144~1836 µg
g-1 wet weight (WW)] were detected in fin samples of
sharks from South Florida31. These findings of BMAA in
aquatic animals at different trophic levels demonstrate an exposure risk
to BMAA through a diet of aquatic products.
The detection of BMAA in the brain tissues of both ALS-PDC patients from
Guam4 and sporadic AD or ALS patients from the United
States32 further support the linkage between BMAA and
neurodegenerative diseases. Additionally, BMAA was shown to be
mis-incorporated into proteins to replace L-serine33and following incorporation could slowly release this toxin as an
endogenous source34.
Vervets
(Chlorocebus sabaeus ) fed a low-dose of BMAA over an extended
period of time in fruit developed neurofibrillary tangles (NFT) and
sparse β-amyloid deposits in the brain in contrast to control animals
that were free from these protein deposits, which indicated that chronic
exposure to the environmental BMAA can trigger neurodegeneration in
vulnerable individuals35. Mathematical models of BMAA
insertion into proteins suggest that the replacement of BMAA for
L-serine in the SOD1 or β-amyloid protein could play a role in
neurodegeneration36.
Although the presence of BMAA in cyanobacterial samples is consistent
across many studies, the quantitation of BMAA in cyanobacterial samples
vary widely and reflects different methods on different
samples37-42. Interestingly, no BMAA was detected from
cyanobacteria isolated from Chinese freshwater environments using
LC-HILIC-MS/MS method38, but BMAA was detected in
diverse mollusks and gastropod from marine ecosystem in China using the
same method29,30. A recent review article described
marine bivalves as having higher concentrations of BMAA, far more than
most fish muscles, but with an exception for shark cartilage, which
hinted that the source of BMAA in aquatic ecosystem requires further
investigations43. In addition, the hypothesis of a
causal relationship between BMAA and neurodegenerative disease
relationship has also been criticized but without primary data and using
selective sources only44. It is clear that additional
studies would benefit this field. In the marine ecosystem in China, the
absence of BMAA detection in cyanobacterial samples but ubiquity in
diverse marine animals30,38 suggests that this may be
a good study case to further examine biomagnification of BMAA.
The Jiaozhou Bay located in the Yellow Sea of China was selected as the
survey area in the present study. Phytoplankton, zooplankton, mollusks,
and crustacea samples were collected during four different seasons and
analyzed for BMAA and its isomers β-aminomethyl-L -alanine (BAMA),
2,4-diaminobutyric acid (DAB) and N -(2-aminoethyl) glycine (AEG)
in marine organisms of different trophic levels using an LC-MS/MS
method. An additional 56 strains (belong to 5 genera) of diatoms
isolated from Chinese seawater were cultured and scanned for these
compounds.
Bioaccumulation
and magnification of BMAA in different marine organisms at different
trophic levels in the Jiaozhou Bay were discussed in the present study.