Impact of Perinatal Arsenic Exposure on Amino Acid Neurotransmitters and Bioenergetics Molecules in the Hippocampus of Rats

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Authors

  • Department of Forensic Science, Sharda University, Greater Noida - 201310, Uttar Pradesh ,IN
  • Department of Biochemistry, MSD Autonomous State Medical College, Bahriach - 271801, Uttar Pradesh ,IN
  • Department of Forensic Science, Sharda University, Greater Noida - 201310, Uttar Pradesh ,IN
  • Institute of Pharmacy, Nirma University, Ahmedabad - 382581, Gujarat ,IN
  • Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh - 11451 ,IN

DOI:

https://doi.org/10.18311/ti/2024/v31i1/34819

Keywords:

Amino Acid Neurotransmitters, Arsenic, Bioenergetics Molecules, Developmental Neurotoxicity, High- Performance Liquid Chromatography

Abstract

Developmental neurotoxicity of Arsenic (As) is a major concern worldwide. High level As exposure is associated with several chronic diseases including adverse pregnancy and birth outcomes. However, very a lack of information on its ability to impair neurodevelopment at lower exposure. To date, there are very few animal studies during the perinatal period of As exposure. Although exposure to As induces developmental neurotoxicity, there is a lack of data regarding its specific effects on amino acid neurotransmitters and bioenergetics biomolecules in the hippocampus of developing rats exposed to As during the perinatal period (GD6-PD21). In continuation of previous studies, rats were exposed to As from gestational day (GD 6) through PD 21 with targeted doses of 0, 2.0, and 4.0 mg/kg/day, respectively. HPLC-UV method was used to estimate the level of amino acid neurotransmitters (aspartate, glutamate, homocysteine, glutamine, serine, and glycine) and the level of Adenosine 5’-Triphosphate (ATP), Adenosine Diphosphate (ADP), Adenosine Monophosphate (AMP), Nicotinamide Mononucleotide (NMN), Nicotinamide Adenine Dinucleotide (NAD+), reduced Nicotinamide Adenine Dinucleotide (NADH) in the hippocampus of rats after the exposure of As. Amino acid neurotransmitter levels, a predictive biomarker of As-induced developmental neurotoxicity were found to be altered. ATP, ADP, and AMP were also significantly impaired in the hippocampus of As-exposed rats. We have observed that the hippocampus is susceptible to As toxicity, both because of the high energy depletion and the alterations in the levels of selected amino acid neurotransmitters. Taken together, our results indicate that perinatal As exposure appears to be critical and vulnerable.

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Published

2024-02-28

How to Cite

Chandravanshi, L. P., Shukla, R. K., Agrawal, P. K., Gupta, R., & Darwish, H. W. (2024). Impact of Perinatal Arsenic Exposure on Amino Acid Neurotransmitters and Bioenergetics Molecules in the Hippocampus of Rats. Toxicology International, 31(1), 55–62. https://doi.org/10.18311/ti/2024/v31i1/34819
Received 2023-08-23
Accepted 2023-12-01
Published 2024-02-28

 

References

Khan KM, Parvez F, Zoeller RT, Hocevar BA, Kamendulis LM, Rohlman D, Eunus M, Graziano J. Thyroid hormones and neurobehavioral functions among adolescents chronically exposed to groundwater with geogenic As in Bangladesh. Sci Total Environ. 2019; 678:278- 87. https://doi.org/10.1016/j.scitotenv.2019.04.426 PMid:31075594 PMCid: PMC6544172 DOI: https://doi.org/10.1016/j.scitotenv.2019.04.426

Alao ME, Perin J, Brooks WA, Hossain L, Goswami D, Zaman K, Yunus M, Khan MA, Jahan Y, Ahmed D, Slavkovich V, Graziano J, Prosperi C, Higdon M, Deloria- Knoll M, O’ Brien KL, George CM. Urinary As is associated with wasting and underweight status in young children in rural Bangladesh. Environ Res. 2021; 195:110025. https:// doi.org/10.1016/j.envres.2020.110025 PMid:32791251 DOI: https://doi.org/10.1016/j.envres.2020.110025

Renzetti S, Cagna G, Calza S, Conversano M, Fedrighi C, Forte G, Giorgino A, Guazzetti S, Majorani C, Oppini M, Peli M, Petrucci F, Pino A, Placidi D, Senofonte O, Zoni S, Alimonti A, Lucchini RG. The effects of exposure to neurotoxic elements on Italian school children behaviour. Sci Rep. 2021; 11(1):9898. https://doi.org/10.1038/s41598- 021-88969-z PMid:33972598 PMCid: PMC8110539 DOI: https://doi.org/10.1038/s41598-021-88969-z

Farzan SF, Karagas MR, Chen Y. In utero and early life As exposure in relation to long-term health and disease. Toxicol Appl Pharmacol. 2013; 272(2):384-90. https://doi. org/10.1016/j.taap.2013.06.030 PMid:23859881 PMCid: PMC3783578 DOI: https://doi.org/10.1016/j.taap.2013.06.030

Tolins M, Ruchirawat M, Landrigan P. The developmental neurotoxicity of As: Cognitive and behavioural consequences of early life exposure. Ann Glob Health. 2014; 80(4):303-14. https://doi.org/10.1016/j.aogh.2014.09.005 PMid:25459332 DOI: https://doi.org/10.1016/j.aogh.2014.09.005

Chandravanshi LP, Gupta R, Shukla RK. As-induced neurotoxicity by dysfunctioning cholinergic and dopaminergic systems in the brain of developing rats. Biol Trace Elem Res. 2019; 189(1):118- 33. https://doi.org/10.1007/s12011-018-1452-5 PMid:30051311 DOI: https://doi.org/10.1007/s12011-018-1452-5

Winterbottom EF, Ban Y, Sun X, Capobianco AJ, Marsit CJ, Chen X, Wang L, Karagas MR, Robbins DJ. Transcriptomewide analysis of changes in the fetal placenta associated with prenatal As exposure in the New Hampshire Birth Cohort Study. Environ Health. 2019; 18(1):100. https://doi.org/10.1186/s12940-019-0535-x PMid:31752878 PMCid: PMC6868717 DOI: https://doi.org/10.1186/s12940-019-0535-x

Martinez VD, Lam WL. Health effects associated with preand perinatal exposure to As. Front Genet. 2021; 12:664717. https://doi.org/10.3389/fgene.2021.664717 PMid:34659330 PMCid: PMC8511415 DOI: https://doi.org/10.3389/fgene.2021.664717

Wang X, Huang X, Zhou L, Chen J, Zhang X, Xu K, Huang Z, He M, Shen M, Chen X, Tang B, Shen L, Zhou Y. Association of As exposure and cognitive impairment: A population-based cross-sectional study in China. Neurotoxicology. 2021; 82:100-7. https://doi.org/10.1016/j. neuro.2020.11.009 PMid:33249123 DOI: https://doi.org/10.1016/j.neuro.2020.11.009

Kile ML, Baccarelli A, Hoffman E, Tarantini L, Quamruzzaman Q, Rahman M, Mahiuddin G, Mostofa G, Hsueh YM, Wright RO, Christiani DC. Prenatal As exposure and DNA methylation in maternal and umbilical cord blood leukocytes. Environ Health Perspect. 2012; 120(7):1061- 6. https://doi.org/10.1289/ehp.1104173 PMid:22466225 PMCid: PMC3404653 DOI: https://doi.org/10.1289/ehp.1104173

Navasumrit P, Chaisatra K, Promvijit J, Parnlob V, Waraprasit S, Chompoobut C, Binh TT, Hai DN, Bao ND, Hai NK, Kim KW, Samson LD, Graziano JH, Mahidol C, Ruchirawat M. Exposure to As in utero is associated with various types of DNA damage and micronuclei in newborns: A birth cohort study. Environ Health. 2019; 18(1):51. https://doi.org/10.1186/s12940-019-0481-7 DOI: https://doi.org/10.1186/s12940-019-0504-4

Chandravanshi LP, Shukla RK, Sultana S, Pant AB, Khanna VK. Early life As exposure and brain dopaminergic alterations in rats. Int J Dev Neurosci. 2014; 38:91-104. https://doi. org/10.1016/j.ijdevneu.2014.08.009 PMid:25179238 DOI: https://doi.org/10.1016/j.ijdevneu.2014.08.009

Ganguly PK, Maddaford TG, Edel AL, O K, Smeda JS, Pierce GN. Increased homocysteine-induced release of excitatory amino acids in the striatum of spontaneously hypertensive stroke-prone rats. Brain Res. 2008; 1226:192-8. https://doi. org/10.1016/j.brainres.2008.05.090 PMid:18598678 DOI: https://doi.org/10.1016/j.brainres.2008.05.090

Amantea D, Bagetta G. Excitatory and inhibitory amino acid neurotransmitters in stroke: From neurotoxicity to ischemic tolerance. Curr Opin Pharmacol. 2017; 35:111-9. https://doi.org/10.1016/j.coph.2017.07.014 PMid:28826602 DOI: https://doi.org/10.1016/j.coph.2017.07.014

Suzuki H, Yamashiro D, Ogawa S, Kobayashi M, Cho D, Iizuka A, Tsukamoto-Yasui M, Takada M, Isokawa M, Nagao K, Fujiwara Y. Intake of seven essential amino acids improves cognitive function and psychological and social function in middle-aged and older adults: A doubleblind, randomized, placebo-controlled trial. Front Nutr. 2020; 7:586166. https://doi.org/10.3389/fnut.2020.586166 PMid:33324669 PMCid: PMC7724102 DOI: https://doi.org/10.3389/fnut.2020.586166

Burnstock G. Purinergic cotransmission. Brain Res Bull. 1999; 50:355–7. https://doi.org/10.1016/S0361- 9230(99)00103-3 PMid:10643434 DOI: https://doi.org/10.1016/S0361-9230(99)00103-3

Ying W. NAD+/NADH and NADP+/NADPH in cellular functions and cell death: Regulation and biological consequences. Antioxid Redox Signal. 2008; 10(2):179-206. https://doi.org/10.1089/ars.2007.1672 PMid:18020963 DOI: https://doi.org/10.1089/ars.2007.1672

Covarrubias AJ, Perrone R, Grozio A, Verdin E. NAD+ metabolism and its roles in cellular processes during ageing. Nat Rev Mol Cell Biol. 2021; 22(2):119-41. https://doi. org/10.1038/s41580-020-00313-x PMid:33353981 PMCid: PMC7963035 DOI: https://doi.org/10.1038/s41580-020-00313-x

Sachdev PS. Homocysteine and brain atrophy. Prog Neuropsychopharmacol Biol Psychiatry. 2005; 29(7):1152- 61. https://doi.org/10.1016/j.pnpbp.2005.06.026 PMid:16102882 DOI: https://doi.org/10.1016/j.pnpbp.2005.06.026

Albrecht J, Sonnewald U, Waagepetersen HS, Schousboe A. Glutamine in the central nervous system: Function and dysfunction. Front Biosci. 2007; 12:332-43. https://doi. org/10.2741/2067 PMid:17127302 DOI: https://doi.org/10.2741/2067

Sharma HS. Interaction between amino acid neurotransmitters and opioid receptors in hyperthermiainduced brain pathology. Prog Brain Res. 2007; 162:295-317. https://doi.org/10.1016/S0079-6123(06)62015-3 PMid:17645925 DOI: https://doi.org/10.1016/S0079-6123(06)62015-3

Shu J, Liu RY, Huang XF. The effects of ear-point stimulation on the contents of somatostatin and Amino acid neurotransmitters in the brain of rats with experimental seizure. Acupunct Electrother Res. 2004; 29(1-2):43-51. https:// doi.org/10.3727/036012904815901498 PMid:15382788 DOI: https://doi.org/10.3727/036012904815901498

Cui T, Qiu HM, Huang D, Zhou QX, Fu XY, Li HY, Jiang XH. Abnormal levels of seven amino neurotransmitters in depressed rat brain and determination by HPLC-FLD. Biomed Chromatogr. 2017; 31(8). https://doi.org/10.1002/bmc.3937 PMid:28097679 DOI: https://doi.org/10.1002/bmc.3937

Zhao XE, He Y, Li M, Chen G, Wei N, Wang X, Sun J, Zhu S, You J. Analysis of amino acid and monoamine neurotransmitters and their metabolites in rat urine of Alzheimer’s disease using in situ ultrasound-assisted derivatization dispersive liquid-liquid microextraction with UHPLC-MS/MS. J Pharm Biomed Anal. 2017; 135:186-98. https://doi.org/10.1016/j.jpba.2016.11.056 PMid:28039808 DOI: https://doi.org/10.1016/j.jpba.2016.11.056

Glowinski J, Axelrod J, Iversen LL. Regional studies of catecholamines in the rat brain. IV. Effects of drugs on the disposition and metabolism of H3-norepinephrine and H3-dopamine. J Pharmacol Exp Ther. 1966; 153(1):30-41.

Huo T, Chang B, Zhang Y, Chen Z, Li W, Jiang H. Alteration of amino acid neurotransmitters in brain tissues of immature rats treated with realgar. J Pharm Biomed Anal. 2012; 57:120- 4. https://doi.org/10.1016/j.jpba.2011.08.032 PMid:21907521 DOI: https://doi.org/10.1016/j.jpba.2011.08.032

Baranowska-Bosiacka I, Dąbrowska-Bouta B, Strużyńska L. Regional changes in purines and selected purinergic receptors in immature rat brain exposed to lead. Toxicology. 2011; 279(1-3):100-7. https://doi.org/10.1016/j. tox.2010.09.016 PMid:20932874 DOI: https://doi.org/10.1016/j.tox.2010.09.016

Yoshino J, Imai S. Accurate measurement of Nicotinamide Adenine Dinucleotide (NAD+) with high-performance liquid chromatography. Methods Mol Biol. 2013; 1077:203-15. https://doi.org/10.1007/978-1-62703-637- 5_14 PMid:24014409 PMCid: PMC3935825 DOI: https://doi.org/10.1007/978-1-62703-637-5_14

Zafra F, Aragón C, Olivares L, Danbolt NC, Giménez C, Storm-Mathisen J. Glycine transporters are differentially expressed among CNS cells. J Neurosci. 1995; 15(5 Pt 2):3952-69. https://doi.org/10.1523/ JNEUROSCI.15-05-03952.1995 PMid:7751957 PMCid: PMC6578198 DOI: https://doi.org/10.1523/JNEUROSCI.15-05-03952.1995

Dutertre S, Becker CM, Betz H. Inhibitory glycine receptors: An update. J Biol Chem. 2012; 287(48):40216-23. https:// doi.org/10.1074/jbc.R112.408229 PMid:23038260 PMCid: PMC3504737 DOI: https://doi.org/10.1074/jbc.R112.408229

Avila A, Nguyen L, Rigo JM. Glycine receptors and brain development. Front Cell Neurosci. 2013; 7:184. https:// doi.org/10.3389/fncel.2013.00184 PMid:24155690 PMCid: PMC3800850 DOI: https://doi.org/10.3389/fncel.2013.00184

Avila A, Vidal PM, Dear TN, Harvey RJ, Rigo JM, Nguyen L. Glycine receptor α2 subunit activation promotes cortical interneuron migration. Cell Rep. 2013; 4(4):738-50. https:// doi.org/10.1016/j.celrep.2013.07.016 PMid:23954789 PMCid: PMC3763372 DOI: https://doi.org/10.1016/j.celrep.2013.07.016

Clark DL, Boutros NN, Mendez MF. The brain and behavior. Cambridge University Press; 2010. p. 21-22. https://doi. org/10.1017/CBO9780511776915

Luengo JG, Muñoz MD, Álvarez-Merz I, Herranz AS, González JC, Martín Del Río R, Hernández-Guijo JM, Solís JM. Intracellular accumulation of amino acids increases synaptic potentials in rat hippocampal slices. Amino Acids. 2019; 51(9):1337-51. https://doi.org/10.1007/s00726-019- 02771-w PMid:31428912 DOI: https://doi.org/10.1007/s00726-019-02771-w

Eid T, Tu N, Lee TS, Lai JC. Regulation of astrocyte glutamine synthetase in epilepsy. Neurochem Int. 2013; 63(7):670-81. https://doi.org/10.1016/j.neuint.2013.06.008 PMid:23791709 PMCid: PMC3825815 DOI: https://doi.org/10.1016/j.neuint.2013.06.008

Rajkowska G, Stockmeier CA. Astrocyte pathology in major depressive disorder: Insights from human postmortem brain tissue. Curr Drug Targets. 2013; 14(11):1225-36. https:// doi.org/10.2174/13894501113149990156 PMid:23469922 PMCid: PMC3799810 DOI: https://doi.org/10.2174/13894501113149990156

Clements JD, Lester RA, Tong G, Jahr CE, Westbrook GL. The time course of glutamate in the synaptic cleft. Science. 1992; 258(5087):1498-501. https://doi.org/10.1126/ science.1359647 PMid:1359647 DOI: https://doi.org/10.1126/science.1359647

Clements JD. Transmitter timecourse in the synaptic cleft: Its role in central synaptic function. Trends Neurosci. 1996; 19(5):163-71. https://doi.org/10.1016/S0166- 2236(96)10024-2 PMid:8723198 DOI: https://doi.org/10.1016/S0166-2236(96)10024-2

Wang Y, Fathali H, Mishra D, Olsson T, Keighron JD, Skibicka KP, Cans AS. Counting the number of glutamate molecules in single synaptic vesicles. J Am Chem Soc. 2019; 141(44):17507-11. https://doi.org/10.1021/jacs.9b09414 PMid:31644274 DOI: https://doi.org/10.1021/jacs.9b09414

Lau A, Tymianski M. Glutamate receptors, neurotoxicity and neurodegeneration. Pflugers Arch. 2010; 460(2):525-42. https://doi.org/10.1007/s00424-010-0809-1 PMid:20229265 DOI: https://doi.org/10.1007/s00424-010-0809-1

Kim PM, Duan X, Huang AS, Liu CY, Ming GL, Song H, Snyder SH. Aspartate racemase, generating neuronal D-aspartate, regulates adult neurogenesis. Proc Natl Acad Sci U S A. 2010; 107(7):3175- 9. https://doi.org/10.1073/pnas.0914706107 PMid:20133766 PMCid: PMC2840285 DOI: https://doi.org/10.1073/pnas.0914706107

D’Aniello G, Tolino A, D’Aniello A, Errico F, Fisher GH, Di Fiore MM. The role of D-aspartic acid and N-methyl-D-aspartic acid in the regulation of prolactin release. Endocrinology. 2000; 141(10):3862- 70. https://doi.org/10.1210/endo.141.10.7706 PMid:11014243 DOI: https://doi.org/10.1210/endo.141.10.7706

Wolosker H, D’Aniello A, Snyder SH. D-aspartate disposition in neuronal and endocrine tissues: Ontogeny, biosynthesis and release. Neuroscience. 2000; 100(1):183-9. https://doi. org/10.1016/S0306-4522(00)00321-3 PMid:10996468 DOI: https://doi.org/10.1016/S0306-4522(00)00321-3

Mattson MP, Shea TB. Folate and homocysteine metabolism in neural plasticity and neurodegenerative disorders. Trends Neurosci. 2003; 26(3):137-46. https://doi.org/10.1016/ S0166-2236(03)00032-8 PMid:12591216 DOI: https://doi.org/10.1016/S0166-2236(03)00032-8

Jaeken J, Detheux M, Fryns JP, Collet JF, Alliet P, Van Schaftingen E. Phosphoserine phosphatase deficiency in a patient with Williams syndrome. J Med Genet. 1997; 34(7):594-6. https://doi.org/10.1136/jmg.34.7.594 PMid:9222972 PMCid: PMC1051004 DOI: https://doi.org/10.1136/jmg.34.7.594

Franke H, Krügel U, Illes P. P2 receptors and neuronal injury. Pflugers Arch. 2006; 452(5):622-44. https://doi. org/10.1007/s00424-006-0071-8 PMid:16645849 DOI: https://doi.org/10.1007/s00424-006-0071-8

Briggs CA, McAfee DA, McCaman RE. Long-term regulation of synaptic acetylcholine release and nicotinic transmission: The role of cyclic AMP. Br J Pharmacol. 1988; 93(2):399-411. https://doi. org/10.1111/j.1476-5381.1988.tb11447.x PMid:2833971 PMCid: PMC1853801 DOI: https://doi.org/10.1111/j.1476-5381.1988.tb11447.x

Vingtdeux V, Davies P, Dickson DW, Marambaud P. AMPK is abnormally activated in tangle- and pre-tangle-bearing neurons in Alzheimer’s disease and other tauopathies. Acta Neuropathol. 2011; 121(3):337-49. https://doi. org/10.1007/s00401-010-0759-x PMid:20957377 PMCid: PMC3060560 DOI: https://doi.org/10.1007/s00401-010-0759-x

Mairet-Coello G, Courchet J, Pieraut S, Courchet V, Maximov A, Polleux F. The CAMKK2-AMPK kinase pathway mediates the synaptotoxic effects of Abeta oligomers through Tau phosphorylation. Neuron. 2013; 78(1):94–108. https://doi. org/10.1016/j.neuron.2013.02.003 PMid:23583109 PMCid: PMC3784324 DOI: https://doi.org/10.1016/j.neuron.2013.02.003