Abstract
Although freshwater planarians are evolutionarily primitive, they are some of the simplest bilateral animals possessing integrated neural networks similar to those in vertebrates. We attempted to develop planarian Dugesia japonica as a model for investigating the neurotoxicity of environmental pollutants such as cadmium (Cd). This study was therefore designed to study the effects of Cd on the locomotor activity, neurobehavior, and neurological enzymes of D. japonica. After planarians were exposed to Cd at high concentrations, altered neurobehavior was observed that exhibited concentration-dependent patterns. Morphological alterations in Cd-treated planarians included irregular shape, body elongation, screw-like hyperkinesia, and bridge-like position. To study the direct effects of Cd on neurological enzymes, tissue homogenates of planarians were incubated in vitro with Cd before their activity was measured. Results showed that acetylcholinesterase (AChE), adenosine triphosphatase (ATPase), and monoamine oxidase A (MAO-A) activities were inhibited in a concentration-dependent manner. MAO-B activity was significantly induced by Cd at low concentrations and inhibited at high concentrations. Changes in the in vivo activity of AChE and ATPase were also found after planarians were treated with Cd at a sublethal concentration (5.56 μM). These observations indicate that neurotransmission systems in planarians are disturbed after Cd exposure.
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Antonio MT, Benito MJ, Leret ML, Corpas I (1998) Gestational administration of cadmium alters the neurotransmitter levels in newborn rat brains. J Appl Toxicol 18:83–88
Beauvais SL, Jones SB, Parris JT, Brewer SK, Little EE (2001) Cholinergic and behavioral neurotoxicity of carbaryl and cadmium to larval rainbow trout (Oncorhynchus mykiss). Ecotoxicol Environ Saf 49:84–90
Best JB, Morita M (1991) Toxicology of planarians. Hydrobiologia 227:375–383
Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254
Buttarelli FR, Pontieri FE, Margotta V, Palladini G (2000) Acetylcholine/dopamine interaction in planaria. Comp Biochem Physiol C 125:225–231
Buttarelli FR, Pellicano C, Pontieri FE (2008) Neuropharmacology and behavior in planarians: translations to mammals. Comp Biochem Physiol C 147:399–408
Calevro F, Filippi C, Deri P, Albertosi C, Batistoni R (1998) Toxic effects of aluminum, chromium, and cadmium in intact and regenerating freshwater planarians. Chemosphere 37:651–659
Carageorgiou H, Katramadou M (2012) Aspects of cadmium neurotoxicity. In: Li YV, Zhang JH (eds) Metal ion in stroke. Springer Science+Business Media, New York, pp 703–750
Carageorgiou H, Tzotzes V, Pantos C, Mourouzis C, Zarros A, Tsakiris S (2004) In vivo and in vitro effects of cadmium on adult rat brain total antioxidant status, acetylcholinesterase, (Na+, K+)-ATPase and Mg2+-ATPase activities: protection by l-cysteine. Basic Clin Pharmacol Toxicol 94:112–118
Carolei A, Margotta V, Palladini G (1975) Proposal of a new model with dopaminergic-cholinergic interactions for neuropharmacological investigations. Neuropsychobiology 1:355–364
Chandra SV, Murthy RC, Husain T, Bansal SK (1984) Effect of interaction of heavy metals on (Na+-K+) ATPase and the uptake of 3H-DA and 3H-NA in rat brain synaptosomes. Acta Pharmacol Toxicol 54:210–213
Cunha I, Mangas-Ramirez E, Guilhermino L (2007) Effects of copper and cadmium on cholinesterase and glutathione S-transferase activities of two marine gastropods. Comp Biochem Physiol C 145:648–657
Du M, Wang D (2009) The neurotoxic effects of heavy metal exposure on GABAergic nervous system in nematode Caenorhabditis elegans. Environ Toxicol Pharmacol 27:314–320
Farrell MS, Gilmore K, Raffa RB, Walker EA (2008) Behavioral characterization of serotonergic activation in the flatworm Planaria. Behav Pharmacol 19:177–182
Gabbiani G, Baid D, Déziel C (1967) Toxicity of cadmium for the central nervous system. Exp Neurol 18:154–160
Grebe E, Schaeffer DJ (1991a) Neurobehavioral toxicity of cadmium sulfate to the planarian Dugesia dorotocephala. Bull Environ Contam Toxicol 46:727–730
Grebe E, Schaeffer DJ (1991b) Planarians in toxicology, standardization of a rapid neurobehavioral toxicity test using phenol in a crossover study. Bull Environ Contam Toxicol 46:866–870
Hernandez R (1989) Na+-K+-ATPase activity possibly regulated by a specific serotonin receptor. Brain Res 408:399–402
Kapu MM, Shaeffer DJ (1991) Planarians in toxicology. Responses of asexual Dugesia dorotocephala to selected metals. Bull Environ Contam Toxicol 47:302–307
Kinne-Saffran E, Hülseweh M, Pfaff C, Kinne RKH (1993) Inhibition of Na, K-ATPase by cadmium: different mechanisms in different species. Toxicol Appl Pharmacol 121:22–29
Kitamura Y, Kakimura J, Taniguchi T (1998) Protective effect of Talipexole on MPTP-treated planarian, a unique Parkinsonian worm model. Jpn J Pharmacol 78:23–29
Lafuente A, Márquez N, Pazo D, Esquifino AI (2001) Cadmium effects on dopamine turnover and plasma levels of prolactin, GH and ACTH. J Physiol Biochem 57:231–236
Lafuente A, González-Carracedo A, Romero A, Cabaleiro T, Esquifino AI (2005) Toxic effects of cadmium on the regulatory mechanism of dopamine and serotonin on prolactin secretion in adult male rats. Toxicol Lett 155:87–96
Leung TKC, Lim L, Lai JCK (1992) Differential effects of metal ions on type A and type B monoamine oxidase activities in rat brain and liver mitochondria. Metab Brain Dis 7:139–146
Li M-H (2012) Survival, mobility, and membrane-bound enzyme activities of freshwater planarian, Dugesia japonica, exposed to synthetic and natural surfactants. Environ Toxicol Chem 31:843–850
Meyer EM, Cooper JR (1981) Correlations between Na+, K+-ATPase activity and acetylcholine release in rat cortical synaptosomes. J Neurochem 36:467–475
Nishimura K, Yamamoto H, Kitamura Y, Agata K (2008) Brain and neural networks. In: Raffa RB, Rawls SM (eds) Planaria: a model for drug action and abuse. Landes Bioscience, Austin, pp 4–12
Northcutt RG (2012) Evolution of centralized nervous systems: two schools of evolutionary thought. Proc Natl Acad Sci USA 109(Suppl 1):10626–10633
Pagán OR, Rowlands AL, Urban KR (2006) Toxicity and behavioral effects of dimethylsulfoxide in planaria. Neurosci Lett 407:274–278
Palladini G, Ruggieri S, Stocchi F, De Pandis MF, Venturini G, Margotta V (1996) A pharmacological study of cocaine activity in planaria. Comp Biochem Physiol C 115:41–45
Pari L, Murugavel P (2007) Diallyl tetrasulfide improves cadmium induced alterations of acetylcholinesterase, ATPase and oxidative stress in brain of rats. Toxicology 234:44–50
Plusquin M, Stevens A-S, Van Belleghem F, Degheselle O, Van Roten A, Vroonen J et al (2012) Physiological and molecular characterization of cadmium stress in Schmidtea mediterranea. Int J Dev Biol 56:183–191
Pretto A, Loro VL, Morsch VM, Moraes BS, Menezes C, Clasen B et al (2010) Acetylcholinesterase activity, lipid peroxidation, and bioaccumulation in silver catfish (Rhamdia quelen) exposed to cadmium. Arch Environ Contam Toxicol 58:1008–1014
Raffa RB, Rawls SM (2008) Planaria: a model for drug action and abuse. Landes Bioscience, Austin
Raffa RB, Holland LJ, Schulingkamp RJ (2001) Quantitative assessment of dopamine D2 antagonist activity using invertebrate (Planaria) locomotion as a functional endpoint. J Pharmacol Toxicol Methods 45:223–226
Raffa RB, Cavallo F, Capasso A (2007) Flumazenil-sensitive dose-related physical dependence in planarians produced by two benzodiazepine and one non-benzodiazepine benzodiazepine receptor agonists. Eur J Pharmacol 564:88–93
Richetti SK, Rosemberg DB, Ventura-Lima J, Monserrat JM, Bogo MR, Bonan CD (2011) Acetylcholinesterase activity and antioxidant capacity of zebrafish brain is altered by heavy metal exposure. Neurotoxicology 32:116–122
Sarnat HB, Netsky MG (2002) When does a ganglion become a brain? Evolutionary origin of the central nervous system. Semin Pediatr Neurol 9:240–253
Sastry BSR, Phillis JW (1977) Antagonism of biogenic amine induced depression of cerebral cortical neurons by Na+-K+-ATPase inhibitors. Can J Physiol Pharmacol 55:170–180
Scheuhammer AM, Cherian MG (1985) Effects of heavy metal cations, sulfhydryl reagents and other chemical agents on striatal D2 dopamine receptors. Biochem Pharmacol 34:3405–3413
Silva KTU, Pathiratne A (2008) In vitro and in vivo effects of cadmium on cholinesterases in Nile tilapia fingerlings: implications for biomonitoring aquatic pollution. Ecotoxicology 17:725–731
Swann AC (1984) Na+, K+-adenosine triphosphatase regulation by the sympathetic nervous system: effects of noradrenergic stimulation and lesion in vivo. J Pharmacol Exp Ther 228:304–311
Tipton KF, Dawson AP (1968) The distribution of monoamine oxidase and α-glycerophosphate dehydrogenase in pig brain. Biochem J 108:95–99
Venturini G, Stocchi F, Margotta V, Ruggieri S, Bravi D, Bellantuono P et al (1989) A pharmacological study of planaria’s dopaminergic receptors. Neuropharmacology 28:1377–1382
Wright RO, Baccarelli A (2007) Metals and neurotoxicology. J Nutr 137:2809–2813
Wu J-P, Chen H-C, Li M-H (2011) The preferential accumulation of cadmium in the head portion of the freshwater planarian, Dugesia japonica (Platyhelminthes: turbellaria). Metallomics 3:1368–1375
Wu J-P, Chen H-C, Li M-H (2012) Bioaccumulation and toxicodynamics of cadmium to freshwater planarian and the protective effect of N-acetylcysteine. Arch Environ Contam Toxicol 63:220–229
Youdim MBH, Collins GGS, Sandler M (1969) Multiple forms of rat brain monoamine oxidase. Nature 223:626–628
Zhou M, Panchuk-Voloshina N (1997) A one-step fluorometric method for the continuous measurement of monoamine oxidase activity. Anal Biochem 253:169–174
Acknowledgments
The authors are grateful for funding support under Grants No. NSC101-2811-B-002-055 and NSC101-2321-B-002-069 from the National Science Council, Taiwan.
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Wu, JP., Lee, HL. & Li, MH. Cadmium Neurotoxicity to a Freshwater Planarian. Arch Environ Contam Toxicol 67, 639–650 (2014). https://doi.org/10.1007/s00244-014-0056-0
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DOI: https://doi.org/10.1007/s00244-014-0056-0