eISSN: 1509-572x
ISSN: 1641-4640
Folia Neuropathologica
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SCImago Journal & Country Rank
1/2018
vol. 56
 
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abstract:
Original paper

Neurotoxic effects of domoic acid on dopaminergic neurons in primary mesencephalic cell culture

Khaled Radad, Mubarak Al-Shraim, Ahmed Al-Emam, Rudolf Moldzio, Wolf-Dieter Rausch

Folia Neuropathol 2018; 56 (1): 39-48
Online publish date: 2018/03/28
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Introduction
Domoic acid is a potent marine neurotoxin produced by certain species of the diatom genus Pseudonitzschia. To our knowledge, there are no studies that have investigated neurotoxic effects of domoic acid on dopaminergic neurons. Accordingly, the present study was carried out to investigate the potential neurotoxic effects of domoic acid on dopaminergic neurons in primary mesencephalic cell culture.

Material and methods
Cultures prepared from embryonic mouse mesencephala (total of 250 embryos) were treated with different concentrations of domoic acid (0.1, 1, 10, 100 µM) on the 10th DIV for 48 h. On the 12th DIV, culture media were used for measurement of lactate dehydrogenase and cultured cells were subjected to immunostaining for tyrosine hydroxylase, neuronal nuclear antigen and glial fibrillary acidic protein, and fluorescence staining using H2DCFDA, JC-1 and DAPI stains. Moreover, roles of AMPA/KA and NMDA receptors in domoic acid neurotoxicity were also investigated.

Results
Domoic acid significantly decreased the number of dopaminergic neurons, decreased the expression of neuronal nuclear antigen and slightly affected astrocyte populations, and increased the release of lactate dehydrogenase into the culture media. AMPA/KA receptor antagonist NBQX but not NMDA receptor antagonist MK-801 significantly inhibited the neurotoxic effect of domoic acid on dopaminergic neurons. H2DCFDA, JC-1 and DAPI fluorescence staining, respectively, revealed that DomA slightly raised ROS production, and significantly decreased mitochondrial membrane potential and increased apoptotic cell death of cultured cells.

Conclusion
The current study presents for the first time the neurotoxic effects of domoic acid on dopaminergic neurons and this effect appears to be attributed to activation of AMPA/KA receptors on dopaminergic neurons.

keywords:

domoic acid, dopaminergic neurons, neurotoxicity, Parkinson’s disease, marine, diatoms

references:
Berman FW, LePage KT, Murray TF. Domoic acid neurotoxicity in cultured cerebellar granule neurons is controlled preferentially by the NMDA receptor Ca(2+) influx pathway. Brain Res 2002; 924: 20-29.
Costa LG, Giordano G, Faustman EM. Domoic acid as a developmental neurotoxin. Neurotoxicology 2010; 31: 409-423.
Gill SS, Hou Y, Ghane T, Pulido OM. Regional susceptibility to domoic acid in primary astrocyte cells cultured from the brain stem and hippocampus. Mar Drugs 2008; 6: 25-38.
Giordano G, White CC, Mohar I, Kavanagh TJ, Costa LG. Glutathione levels modulate domoic acid induced apoptosis in mouse cerebellar granule cells. Toxicol Sci 2007; 100: 433-444.
Giordano G, Klintworth HM, Kavanagh TJ, Costa LG. Apoptosis induced by domoic acid in mouse cerebellar granule neurons involves activation of p38 and JNK MAP kinases. Neurochem Int 2008; 52: 1100-1105.
Hiolski EM, Ito S, Beggs JM, Lefebvre KA, Litke AM, Smith DR. Domoic acid disrupts the activity and connectivity of neuronal networks in organotypic brain slice cultures. Neurotoxicology 2016; 56: 215-224.
Jandová K, Kozler P, Langmeier M, Marešová D, Pokorný J, Riljak V. Influence of low-dose neonatal domoic acid on the spontaneous behavior of rats in early adulthood. Physiol Res 2014; 63: 521-528.
Jeffery B, Barlow T, Moizer K, Paul S, Boyle C. Amnesic shellfish poison. Food Chem Toxicol 2004; 42: 545-557.
Lan AP, Chen J, Chai ZF, Hu Y. The neurotoxicity of iron, copper and cobalt in Parkinson’s disease through ROS-mediated mechanisms. Biometals 2016; 29: 665-678.
Larm JA, Beart PM, Cheung NS. Neurotoxin domoic acid produces cytotoxicity via kainate- and AMPA-sensitive receptors in cultured cortical neurones. Neurochem Int 1997; 31: 677-82.
Li S, Dong J, Cheng C, Le W. Therapies for Parkinson’s disease: alternative to current pharmacological interventions. Neural Transm 2016; 123: 1279-1299.
Mayer AM, Hall M, Fay MJ, Lamar P, Pearson C, Prozialeck WC, Lehmann VK, Jacobson PB, Romanic AM, Uz T, Manev H. Effect of a short-term in vitro exposure to the marine toxin domoic acid on viability, tumor necrosis factor-alpha, matrix metalloproteinase-9 and superoxide anion release by rat neonatal microglia. BMC Pharmacol 2001; 1: 7.
Pérez-Gómez A, Cabrera-García D, Warm D, Marini AM, Salas Puig J, Fernández-Sánchez MT, Novelli A. Selective Enhancement of Domoic Acid Toxicity in Primary Cultures of Cerebellar Granule Cells by Lowering Extracellular Na+ Concentration. Toxicol Sci 2018; 161: 103-114.
Perl TM, Bédard L, Kosatsky T, Hockin JC, Todd EC, Remis RS. An outbreak of toxic encephalopathy caused by eating mussels contaminated with domoic acid. N Engl J Med 1990; 322: 1775-1780.
Pinto-Silva CR, Moukha S, Matias WG, Creppy EE. Domoic acid induces direct DNA damage and apoptosis in Caco-2 cells: recent advances. Environ Toxicol 2008; 23: 657-663.
Quilliam MA, Wright JL. The amnesic shellfish poisoning mystery. Anal Chem 1989; 61: 1053A-106A.
Radad K, Moldzio R, Rausch WD. Rapamycin protects dopaminergic neurons against rotenone-induced cell death in primary mesencephalic cell culture. Folia Neuropathol 2015; 53: 250-261.
Ramya EM, Kumar GP, Anand T, Anilakumar KR. Modulatory effects of Terminalia arjuna against domoic acid induced toxicity in Caco-2 cell line. Cytotechnology 2017; 69: 725-739.
Schapira AH. Etiology of Parkinson’s disease. Neurology 2006; 66: 10-23.
Scott L, Dawson VL, Dawson TM. Trumping neurodegeneration: Targeting common pathways regulated by autosomal recessive Parkinson’s disease genes. Exp Neurol 2017; 298: 191-201.
Tysnes OB, Storstein A. Epidemiology of Parkinson’s disease. J Neural Transm 2017; 124: 901-905.
Vieira AC, Alemañ N, Cifuentes JM, Bermúdez R, Peña ML, Botana LM. Brain Pathology in Adult Rats Treated With Domoic Acid. Vet Pathol 2015; 52: 1077-1086.
Vieira AC, Cifuentes JM, Bermúdez R, Ferreiro SF, Castro AR, Botana LM. Heart Alterations after Domoic Acid Administration in Rats. Toxins (Basel) 2016; 8: 3.
Xu R, Tao Y, Wu C, Yi J, Yang Y, Yang R, Hong D. Domoic acid induced spinal cord lesions in adult mice: evidence for the possible molecular pathways of excitatory amino acids in spinal cord lesions. Neurotoxicology 2008; 29: 700-707.
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