title: Pharmacological studies confirm neurotoxic metabolite(s) produced by the bloom-forming Cylindrospermopsis raciborskii in Hungary.
abstract: A rapid cyanobacterial bloom of Cylindrospermopsis raciborskii (3.2 × 10(4) filaments/mL) was detected early November, 2012, in the Fancsika pond (East Hungary). The strong discoloration of water was accompanied by a substantial fish mortality (even dead cats were seen on the site), raising the possibility of some toxic metabolites in the water produced by the bloom-forming cyanobacteria (C. raciborskii). The potential neuronal targets of the toxic substances in the bloom sample were studied on identified neurons (RPas) in the central nervous system of Helix pomatia. The effects of the crude aqueous extracts of the Fancsika bloom sample (FBS) and the laboratory isolate of C. raciborskii from the pond (FLI) were compared with reference samples: C. raciborskii ACT 9505 (isolated in 1995 from Lake Balaton, Hungary), the cylindrospermopsin producer AQS, and the neurotoxin (anatoxin-a, homoanatoxin-a) producer Oscillatoria sp. (PCC 6506) strains. Electrophysiological tests showed that both FBS and FLI samples as well the ACT 9505 extracts modulate the acetylcholine receptors (AChRs) of the neurons, evoking ACh agonist effects, then inhibiting the ACh-evoked neuronal responses. Dose-response data suggested about the same range of toxicity of FBS and FLI samples (EC50  = 0.397 mg/mL and 0.917 mg/mL, respectively) and ACT 9505 extracts (EC50  = 0.734 mg/mL). The extract of the neurotoxin-producing PCC 6506 strain, however, proved to be the strongest inhibitor of the ACh responses on the same neurons (EC50  = 0.073 mg/mL). The presented results demonstrated an anatoxin-a-like cholinergic inhibitory effects of cyanobacterial extracts (both the environmental FBS sample, and the laboratory isolate, FLI) by some (yet unidentified) toxic components in the matrix of secondary metabolites. Previous pharmacological studies of cyanobacterial samples collected in other locations (Balaton, West Hungary) resulted in similar conclusions; therefore, we cannot exclude that this chemotype of C. raciborskii which produce anatoxin-a like neuroactive substances is more widely distributed in this region.
authors.affiliation: Department of Experimental Zoology, MTA Centre for Ecological Research, Balaton Limnological Institute, H-8237, Tihany, POB 35, Hungary.
authors.forename: Á
authors.initials: Á
authors.lastname: Vehovszky
authors.forename: A W
authors.initials: AW
authors.lastname: Kovács
authors.forename: A
authors.initials: A
authors.lastname: Farkas
authors.forename: J
authors.initials: J
authors.lastname: Győri
authors.forename: H
authors.initials: H
authors.lastname: Szabó
authors.forename: G
authors.initials: G
authors.lastname: Vasas
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000470:Alkaloids; D000818:Animals; D001427:Bacterial Toxins / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity; D000087522:Cyanobacteria Toxins; D046891:Cylindrospermopsis / Q000187:drug effects / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005068:Eutrophication; D006372:Helix, Snails; D006814:Hungary; D060106:Lakes; D009474:Neurons / Q000187:drug effects; D009498:Neurotoxins / Q000096:biosynthesis* / Q000633:toxicity*; D054300:Oscillatoria / Q000737:chemistry / Q000378:metabolism; D011950:Receptors, Cholinergic / Q000187:drug effects; D014326:Tropanes / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity; D014498:Uracil / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000633:toxicity
chemical_list: D000470:Alkaloids; D001427:Bacterial Toxins; D019086:Bridged Bicyclo Compounds, Heterocyclic; D000087522:Cyanobacteria Toxins; D009498:Neurotoxins; D011950:Receptors, Cholinergic; D014326:Tropanes; C524097:homoanatoxin-a; C089595:cylindrospermopsin; D014498:Uracil; C509783:anatoxin a; D000109:Acetylcholine
keywords: Helix pomatia; acetylcholine; bloom sample; cyanobacteria; fish mortality