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

Sci Rep. 2018 Feb 2;8(1):2308. doi: 10.1038/s41598-018-20327-y.

Abstract

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.

MeSH terms

  • Amino Acids, Diamino / administration & dosage
  • Amino Acids, Diamino / toxicity*
  • Animals
  • Cognition / drug effects*
  • Cyanobacteria Toxins
  • Enzyme Inhibitors / administration & dosage
  • Enzyme Inhibitors / toxicity*
  • Excitatory Amino Acid Agonists / administration & dosage
  • Excitatory Amino Acid Agonists / toxicity*
  • Injections, Subcutaneous
  • Kidney / pathology
  • Lethal Dose 50
  • Liver / pathology
  • Liver Function Tests
  • Male
  • Marine Toxins
  • Memory / drug effects
  • Mice, Inbred C57BL
  • Microcystins / administration & dosage
  • Microcystins / toxicity*
  • Spatial Learning / drug effects
  • Survival Analysis

Substances

  • Amino Acids, Diamino
  • Cyanobacteria Toxins
  • Enzyme Inhibitors
  • Excitatory Amino Acid Agonists
  • Marine Toxins
  • Microcystins
  • beta-N-methylamino-L-alanine
  • cyanoginosin LR