New research shows that 2,4-DABA induces irreversible functional changes in neurons.

From the abstract of a recent paper by Spacic et al. in Aquatic Toxicology:

“In this paper we present, for the first time, a detailed account of electrophysiological effects of 2,4-diaminobutyric acid (2,4-DABA). 2,4-DABA is a neurotoxic non-protein amino acid produced by Cyanobacteria with a possible link to neurodegenerative disorders in animals and humans. Intracellular recordings were performed on Retzius nerve cells of the leech Haemopis sanguisuga using glass microelectrodes filled with 3 mol/L KCl. Our results show that 2,4-DABA is an excitatory amino acid, causing membrane depolarization in a concentration dependent manner. The most prominent depolarizations of 39.63 ± 2.22 mV and 47.05 ± 4.33 mV, induced by 5 × 10−3 and 10−2 mol/L 2,4-DABA respectively, are several times larger than maximal depolarizations induced by either Glutamate, Aspartate, β-N-methylamino-alanine (BMAA) or β-N-oxalylamino-alanine (BOAA) on our model. These 2,4-DABA induced depolarizations evolve through two distinct stages, which is a novel phenomenon in electrical cell activity upon application of an excitatory amino acid, at least on our model. Involvement of two separate mechanisms, suggested by the two stage phenomenon, is discussed in the paper. We also provide evidence that 2,4-DABA induces irreversible functional disturbances in neurons in a concentration dependent manner, since only half of the cells recovered normal electrical activity after application of 5 × 10−3 mol/L 2,4-DABA, and none recovered after application of 10−2 mol/L 2,4-DABA. Effects of both L-2,4-DABA and DL-2,4-DABA were tested and are not significantly different.”

Reference:

S. Spasic, M. Stanojevic, J. Nesovic Ostojic, S. Kovacevic, M. Prostran, S. Lopicic (2018).
Extensive depolarization and lack of recovery of leech Retzius neurons caused by 2,4 diaminobutyric acid. Aquatic Toxicology, Volume 199, Pages 269-275. https://doi.org/10.1016/j.aquatox.2018.03.036.

The paper acknowledges CYANOCOST.

Microcystins, BMAA and BMAA isomers in 100-year-old Antarctic cyanobacterial mats collected during Captain R.F. Scott’s Discovery Expedition

From the abstract of a new paper by Jungblut et. al (2018) published in European Journal of Phycology :

Microcystins (MCN), β-N-methylamino-L-alanine (BMAA) and anatoxin-a were investigated in Antarctic cyanobacterial mats collected from Ross Island and the McMurdo Ice Shelf, East Antarctica during Captain Scott’s ‘Discovery’ National Antarctic Expedition (1901–1904). Ultra-performance liquid chromatography-photodiode array detection (UPLC-PDA) and tandem mass spectrometry (MS/MS) analysis were used to quantify the cyanotoxins in seven cyanobacterial mat samples. MCNs were identified in six of the mat samples at concentrations from 0.5 to 16.1 µg g–1 dry weight. BMAA was found in one sample (528 ng g–1 dry weight, total BMAA), as well as two BMAA isomers, 2,4-diaminobutyric acid (DAB) and N-(2-aminoethyl) glycine (AEG) in six samples up to 6.56 and 6.79 μg g–1 dry weight, respectively. No anatoxin-a was detected. The findings confirm that MCNs, BMAA and BMAA isomers are preserved under dry herbarium conditions. The ‘Discovery’ cyanobacterial mat samples represent the oldest polar cyanobacterial samples found to contain cyanotoxins to date and provide new baseline data for cyanotoxins in Antarctic freshwater cyanobacterial mats from prior to human activity in Antarctica, the development of the ozone hole and current levels of climatic change.

Read the story by Katie Pavid in the Natural History Museum, UK website.

Reference:

A.D. Jungblut, J. Wilbraham, S.A. Banack, J.S. Metcalf & G.A. Codd (2018) Microcystins, BMAA and BMAA isomers in 100-year-old Antarctic cyanobacterial mats collected during Captain R.F. Scott’s Discovery Expedition, European Journal of Phycology, DOI: 10.1080/09670262.2018.1442587

Repeated five-day administration of L-BMAA, microcystin-LR, or as mixture, in adult C57BL/6 mice – lack of adverse cognitive effects

Abstract from the Myhre et al. (2018) paper in Scientific Reports:

“The cyanobacterial toxins β-methylamino-L-alanine (L-BMAA) and microcystin-LR (MC-LR; a potent liver toxin) are suspected to cause neurological disorders. Adult male C57BL/6JOlaHsd mice aged approximately 11 months were subcutaneously injected for five consecutive days with L-BMAA and microcystin-LR alone, or as a mixture. A dose-range study determined a tolerable daily dose to be ~31 µg MC-LR/kg BW/day based on survival, serum liver status enzymes, and relative liver and kidney weight. Mice tolerating the first one-two doses also tolerated the subsequent three-four doses indicating adaptation. The LD50 was 43–50 μg MC-LR/kg BW. Long-term effects (up to 10 weeks) on spatial learning and memory performance was investigated using a Barnes maze, were mice were given 30 µg MC-LR/kg BW and/or 30 mg L-BMAA/kg BW either alone or in mixture for five consecutive days. Anxiety, general locomotor activity, willingness to explore, hippocampal and peri-postrhinal cortex dependent memory was investigated after eight weeks using Open field combined with Novel location/Novel object recognition tests. Toxin exposed animals did not perform worse than controls, and MC-LR exposed animals performed somewhat better during the first Barnes maze re-test session. MC-LR exposed mice rapidly lost up to ~5% body weight, but regained weight from day eight.”

Reference:

Oddvar Myhre, Dag Marcus Eide, Synne Kleiven, Hans Christian Utkilen & Tim Hofer (2018), Scientific Reports 8, Article number: 2308. doi:10.1038/s41598-018-20327-y

 

Metabolic solutions to the biosynthesis of BMAA and 2,4-DAB in cyanobacteria

The pathways of BMAA (and the related 2,4-DAB) biosynthesis in cyanobacteria are not known. A recent review by Peter Nunn and Geoffrey Codd considers possible metabolic routes, by analogy with reactions used in other species, by which these amino acids might be biosynthesised by cyanobacteria, which are a widespread potential environmental source of these neurotoxins.

Reference: Nunn, P. B. and Codd, G. A. (2017). “Metabolic solutions to the biosynthesis of some diaminomonocarboxylic acids in nature: Formation in cyanobacteria of the neurotoxins 3-N-methyl-2,3-diaminopropanoic acid (BMAA) and 2,4-diaminobutanoic acid (2,4-DAB)”. Phytochemistry 144, 253-270.

https://doi.org/10.1016/j.phytochem.2017.09.015