Effect of Valproic Acid on Morphology and Behavior of <i>Hydra viridissima</i>: Possibility of using Hydra</i> for Screening Neuromodulators





Battery Cell Complex, Chloro Hydra, Cnidarians


Nervous system of Hydra responds to mechanical, chemical, light and temperature stimuli, despite lack of organizational complexities like ganglion or sense organs. Nerve net of Hydrashows remarkable similarities with vertebrates at cellular and molecular level. Chemical and electrical synapses of Hydramodulate array of behavioral responses exhibited by Hydra. We have assayed toxicity and tested effect of Valproic Acid (VPA), an anti-epileptic drug on Hydra. We have performed whole animal toxicity testing, cytological staining using toluidine blue and assayed feeding behavior post VPA treatment. We conclude mild toxicity and loss of cell organization pattern in tentacles of Hydraupon prolonged VPA exposure. Our results indicate the possibility of using invertebrates like Hydrafor screening of chemical modulators of molecular pathways.


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Bosch TCG. Rethinking the role of immunity: Lessons from Hydra. Trends Immunol. 2014; 35:495–502. PMid: 25174994. https://doi.org/10.1016/j.it.2014.07.008

Westfall J, Yamataka S, Enos PD. Ultrastructural evidence of polarized synapses in the nerve net of Hydra. The J Cell Biol. 1971; 51:318–23. PMid: 5111879 https://doi. org/10.1083/jcb.51.1.318

Kass-Simon G, Pierobon P. Cnidarian chemical neurotransmission, an updated overview. Comp Biochem Physiol Part A Mol Integr Physiol. 2007; 146:9–25. PMid: 17101286.https://doi.org/10.1016/j.cbpa.2006.09.008

Pierobon P. Coordinated modulation of cellular signaling through ligand-gated ion channels in Hydra vulgaris (Cnidaria, Hydrozoa ). Int J Dev Biol. 2012; 565:551–65. PMid: 22689363. https://doi.org/10.1387/ijdb.113464pp

Pierobon P. Regional modulation of the response to glutathione in Hydra vulgaris. J Exp Bio. 2015; 218:2226–32. PMid: 25987735. https://doi.org/10.1242/jeb.120311

Assmann M. Peptide-gated ion channels and the simple nervous system of Hydra. J Exp Bio. 2015; 218:551–61. PMid: 25696818. https://doi.org/10.1242/jeb.111666

Bosch TCG, Klimovich A, Domazet-Loso T, Grunder S, Holstein TW, Jekely G, Miller DJ, Murillo-Rincon AP, Rentzsch F, Richards GS, Schroder K, Technau U, Yuste R. Back to the Basics: Cnidarians Start to Fire. Trends Neurosci. 2017; 40:92–105. PMid: 28041633 PMCid: PMC5285349. https://doi.org/10.1016/j.tins.2016.11.005

Dupre C, Yuste R, Dupre C, Yuste R. Non-overlapping Neural Networks in Hydra vulgaris article non-overlapping neural networks in Hydra vulgaris. Curr Biol. 2017; 27(8):1085–7. PMid: 28366745 PMCid: PMC5423359. https://doi. org/10.1016/j.cub.2017.02.049

Quinn B, Gagne F, Blaise C. Hydra, a model system for environmental studies. Int J Dev Biol. 2012; 625;613–25. PMid: 22689364. https://doi.org/10.1387/ijdb.113469bq

Murugadas A, Zeeshan M, Thamaraiselvi K, Ghaskadbi S, Akbarsha MA. Hydra as a model organism to decipher the toxic effects of copper oxide nanorod: Eco-toxicogenomics approach. Sci Rep. 2016; 6:1–14. PMid: 27417574 PMCid: PMC4945869. https://doi.org/10.1038/srep29663

Berking S. Effects of the anticonvulsant drug Valproic Acid and related substances on developmental processes in hydroids. Toxicol Vitr. 1991; 5:109–17. https://doi.org/10.1016/0887-2333(91)90030-H

Fagundes SBR. Valporoic acid: Review. Rev Neurociencias.2008; 16:130–6.

Ting R, Fei W, Danmou X, Zhengren P, Dong R, Wei F, Yan C, Zhiming Z, Huan W, Junweng W, Wusheng K, Qingsong Z. Effects of Valproic Acid on axonal regeneration and recovery of motor function after peripheral nerve injury in the rat. Arch Bone Jt Surg. 2014; 2(1):17–24.

Bossert P, Galliot B. How to use Hydra as a model system to teach biology in the classroom. Int J Dev Biol. 2012; 56:637– 52. PMid: 22689377. https://doi.org/10.1387/ijdb.123523pb

Kulkarni R, Galande S. Measuring glutathione-induced feeding response in Hydra. JOVE. 2014; 93:e52178. PMid: 25490534 PMCid: PMC4354099. https://doi.org/10.3791/52178

Traversetti L, Del-Grosso F, Malafoglia V, Colasanti M, Ceschin S, Larsen S, Scalici M. The Hydra regeneration assay reveals ecological risks in running waters: A new proposal to detect environmental teratogenic threats.Ecotoxicology. 2017; 28(2):184–95. PMid: 27995409. https://doi.org/10.1007/s10646-016-1753-4

Grosvenor W, Rhoads DE, Kass-Simon G. Chemoreceptive control of feeding processes in Hydra. Chem Senses.1996; 21:313–21. PMid: 8670710. https://doi.org/10.1093/ chemse/21.3.313

Carter JA, Hyland C, Steele RE, Collins ES. Dynamics of mouth opening in Hydra. Biophysj. 2016; 110:1191– 201. PMid: 26958895 PMCid: PMC4788721.https://doi.org/10.1016/j.bpj.2016.01.008

Chapman GB, Tilney LG. Cytological studies of the nematocysts of Hydra II. The stenoteles. J Biophys Biochem Cytol. 1959; 5:79–84. PMid: 13630937. https://doi.org/10.1083/jcb.5.1.79

Scappaticci AA, Kass-Simon G. NMDA and GABAB receptors are involved in controlling nematocyst discharge in Hydra. Comp Biochem Physiol Part A Mol Integr Physiol. 2008; 150:415–22. PMid: 18524656. https://doi.org/10.1016/j.cbpa.2008.04.606

Scappaticci AA, Kahn F, Kass-Simon G. Nematocyst discharge in Hydra vulgaris: Differential responses of desmonemes and stenoteles to mechanical and chemical stimulation. Comp Biochem Physiol Part A Mol Integr Physiol. 2010; 157:184–91. PMid: 20601054. https://doi.org/10.1016/j.cbpa.2010.06.177

Kass-Simon G, Scappaticci AA. The behavioral and developmental physiology of nematocysts. Can J Zool, 2002;80:1772–94. https://doi.org/10.1139/z02-135

Holstein TWA. A view to kill. BMC Biol. 2012; 10:2–5.PMid: 22390773 PMCid: PMC3293708. https://doi.


Johannessen CU. Mechanisms of action of valproate: A commentatory. Neurochem Int. 2000; 37:103–10. https:// doi.org/10.1016/S0197-0186(00)00013-9

Phiel CJ, Zhang F, Huang EY, Guenther MG, Lazar MA, Klein PS. Histone deacetylase is a direct target of Valproic Acid, a potent anticonvulsant, mood stabilizer and teratogen.J Biol Chem. 2001; 276:36734– 41. PMid: 11473107.https://doi.org/10.1074/jbc.M101287200

Bose P, Dai Y, Grant S. Histone Deacetylase Inhibitor (HDACI) mechanisms of action: Emerging insights. Pharmacol Ther.2014; 31:477–9. PMid: 24769080 PMCid: PMC4117710. https://doi.org/10.1016/j.pharmthera.2014.04.004

Bosch TCG, Anton-Erxleben F, Hemmrich G, Khalturin K. The Hydra polyp: Nothing but an active stem cell community. Dev Growth Differ. 2010; 52:15–25. PMid: 19891641. https://doi.org/10.1111/j.1440-169X.2009.01143.x



How to Cite

Alphonso, S., Pandit, P., Ramachandran, H., & Kulkarni, A. (2019). Effect of Valproic Acid on Morphology and Behavior of <i>Hydra viridissima</i>: Possibility of using Hydra</i> for Screening Neuromodulators. Toxicology International, 25(2), 116–123. https://doi.org/10.18311/ti/2018/v25i2/23086



Original Research