Theoretical and Natural Science

- The Open Access Proceedings Series for Conferences


Theoretical and Natural Science

Vol. 16, 04 December 2023


Open Access | Article

Effects of sucralose on learning and memory in Caenorhabditis Elegans

Houze Yang * 1
1 The Experimental High School Attached To Beijing Normal University

* Author to whom correspondence should be addressed.

Theoretical and Natural Science, Vol. 16, 25-41
Published 04 December 2023. © 2023 The Author(s). Published by EWA Publishing
This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Citation Houze Yang. Effects of sucralose on learning and memory in Caenorhabditis Elegans. TNS (2023) Vol. 16: 25-41. DOI: 10.54254/2753-8818/16/20240509.

Abstract

Sugar-substituted beverages, including those sweetened with sucralose, are popular as sugar-free alternatives. However, the impact of sucralose on learning and memory abilities remains inconclusive. This study aimed to investigate the effects and mechanisms of sucralose, a commonly used sugar substitute, on the learning and memory abilities of Caenorhabditis elegans. Three different concentrations of sucralose were administered to C. elegans at the developmental stage to observe the effects on their non-associative and associative learning abilities. Non-associative learning was assessed through tap stimulus and odor chemotaxis assays, while associative learning was measured using a combination of high NaCl concentration and starvation-induced chemotaxis response. RT-qPCR analysis was employed to detect changes in the expression of 11 learning and memory-related genes in C. elegans exposed to sucralose, and homology analysis was conducted to compare these genes with their human counterparts. The results showed that C. elegans treated with a high concentration of sucralose exhibited significantly prolonged withdrawal reaction times, while those treated with a low concentration displayed reduced odor chemotaxis. Additionally, nematodes treated with different sucralose concentrations demonstrated impaired associative learning ability. RT-qPCR analysis revealed a significant down-regulation in the relative expression of all genes following high sucralose treatment, with the glutamate receptor signaling pathway being the most affected. Homology analysis indicated that 10 out of the 11 genes had homologs in humans. In conclusion, this study suggests that high concentrations of sucralose can diminish the learning and memory abilities of nematodes by extensively modulating learning and memory-related pathways, particularly affecting the glutamate receptor signaling pathway.

Keywords

Sugar Substitutes, Sucralose, C. Elegans, Learning, Memory

References

1. E. M. Navarrete-Munoz et al., “Sweet-beverage consumption and risk of pancreatic cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC),” American Journal of Clinical Nutrition, vol. 104, no. 3, pp. 760-768, Sep 2016, doi: 10.3945/ajcn.116.130963.

2. J. J. Anderson et al., “The associations of sugar-sweetened, artificially sweetened and naturally sweet juices with all-cause mortality in 198,285 UK Biobank participants: a prospective cohort study,” Bmc Medicine, vol. 18, no. 1, Apr 2020, Art no. 97, doi: 10.1186/s12916-020-01554-5.

3. D. Martyn et al., “Low-/No-Calorie Sweeteners: A Review of Global Intakes,” Nutrients, vol. 10, no. 3, Mar 2018, Art no. 357, doi: 10.3390/nu10030357.

4. K. Noda, K. Nakayama, and T. Oku, “Serum Glucose and Insulin Levels and Erythritol Balance after Oral-Administration of Erythritol in Healthy-Subjects,” European Journal of Clinical Nutrition, vol. 48, no. 4, pp. 286-292, Apr 1994. [Online]. Available: <Go to ISI>://WOS:A1994NG43700008.

5. M. Libik-Konieczny et al., “Steviol glycosides profile inStevia rebaudianaBertoni hairy roots cultured under oxidative stress-inducing conditions,” Applied Microbiology and Biotechnology, vol. 104, no. 13, pp. 5929-5941, Jul 2020, doi: 10.1007/s00253-020-10661-5.

6. C. Gardana, P. Simonetti, E. Canzi, R. Zanchi, and P. Pietta, “Metabolism of stevioside and rebaudioside A from Stevia rebaudiana extracts by human microflora,” Journal of Agricultural and Food Chemistry, vol. 51, no. 22, pp. 6618-6622, Oct 2003, doi: 10.1021/jf0303619.

7. K. Rycerz and J. E. Jaworska-Adamu, “Effects of aspartame metabolites on astrocytes and neurons,” Folia Neuropathologica, vol. 51, no. 1, pp. 10-17, 2013, doi: 10.5114/fn.2013.34191.

8. E. Gardner, “ALTERNATIVE SUGARS Sucralose,” British Dental Journal, vol. 224, no. 1, pp. 5-5, Jan 2018, doi: 10.1038/sj.bdj.2018.15.

9. S. G. Wood, B. A. John, and D. R. Hawkins, “The pharmacokinetics and metabolism of sucralose in the dog,” Food and Chemical Toxicology, vol. 38, pp. S99-S106, 2000. [Online]. Available: <Go to ISI>://WOS:000088118800010.

10. G. V. Research. “Diet Soft Drinks Market Size, Share & Trends Analysis Report By Distribution Channel (Supermarkets & General Merchandise, Online), By Region, And Segment Forecasts.” https://www.grandviewresearch.com/industry-analysis/diet-soft-drinks-market (accessed September 10, 2023).

11. China Baogao. “China Sugar Free Drinks Industry Development Status Research and Investment Trend Forecast Report(2022-2029.” https://www.chinabaogao.com/baogao/202210/ 614514.html (accessed September 10, 2023).

12. M. Witkowski et al., “The artificial sweetener erythritol and cardiovascular event risk,” Nature Medicine, 2023 Feb 2023, doi: 10.1038/s41591-023-02223-9.

13. E. Harris, “Experts Disagree About Aspartame’s “Possibly Carcinogenic” Status,” Jama-Journal of the American Medical Association, 2023 Jul 2023, doi: 10.1001/jama.2023.13132.

14. Lazarov and C. Hollands, “Hippocampal neurogenesis: Learning to remember,” Progress in Neurobiology, vol. 138, pp. 1-18, Mar-May 2016, doi: 10.1016/j.pneurobio.2015.12.006.

15. Erbas et al., “Evaluation of long-term effects of artificial sweeteners on rat brain: a biochemical, behavioral, and histological study,” Journal of Biochemical and Molecular Toxicology, vol. 32, no. 6, Jun 2018, Art no. e22053, doi: 10.1002/jbt.22053.

16. M. A. Lebda, K. M. Sadek, and Y. S. El-Sayed, “Aspartame and Soft Drink-Mediated Neurotoxicity in Rats: Implication of Oxidative Stress, Apoptotic Signaling Pathways, Electrolytes and Hormonal Levels,” Metabolic Brain Disease, vol. 32, no. 5, pp. 1639-1647, Oct 2017, doi: 10.1007/s11011-017-0052-y.

17. X. Li, G. P. Dong, G. X. Han, L. P. Du, and M. Y. Li, “Zebrafish Behavioral Phenomics Links Artificial Sweetener Aspartame to Behavioral Toxicity and Neurotransmitter Homeostasis,” Journal of Agricultural and Food Chemistry, vol. 69, no. 50, pp. 15393-15402, Dec 2021, doi: 10.1021/acs.jafc.1c06077.

18. J. P. Finn and G. H. Lord, “Neurotoxicity studies on sucralose and its hydrolysis products with special reference to histopathologic and ultrastructural changes,” Food and Chemical Toxicology, vol. 38, pp. S7-S17, 2000. [Online]. Available: <Go to ISI>://WOS:000088118800003.

19. F. Yang et al., “Food nutritional evaluation: Caenorhabditis elegans as a model organism,” Shipin Kexue / Food Science, vol. 40, no. 11, pp. 268-276, 2019. [Online]. Available: <Go to ISI>://CABI:20193357634.

20. N. Zhao, C. Ren, H. Liu, and C. Zhang, “Current progress on the methods for studying learning behavior of Caenorhabditis elegans,” Journal of Northwest A & F University - Natural Science Edition, vol. 37, no. 11, pp. 55-61, 2009. [Online]. Available: <Go to ISI>://CABI:20093354966.

21. C. H. Rankin, C. D. O. Beck, and C. M. Chiba, “CAENORHABDITIS-ELEGANS - A NEW MODEL SYSTEM FOR THE STUDY OF LEARNING AND MEMORY,” Behavioural Brain Research, vol. 37, no. 1, pp. 89-92, Feb 1990, doi: 10.1016/0166-4328(90)90074-o.

22. Y. Wang et al., “Aesculin offers increased resistance against oxidative stress and protective effects against A beta-induced neurotoxicity in Caenorhabditis elegans,” European Journal of Pharmacology, vol. 917, Feb 2022, Art no. 174755, doi: 10.1016/j.ejphar.2022.174755.

23. C. I. Bargmann, E. Hartwieg, and H. R. Horvitz, “ODORANT-SELECTIVE GENES AND NEURONS MEDIATE OLFACTION IN C-ELEGANS,” Cell, vol. 74, no. 3, pp. 515-527, Aug 1993, doi: 10.1016/0092-8674(93)80053-h.

24. R. Chandra et al., “Sleep is required to consolidate odor memory and remodel olfactory synapses,” Cell, vol. 186, no. 13, pp. 2911-+, Jun 2023, doi: 10.1016/j.cell.2023.05.006.

25. V. Raj and A. Thekkuveettil, “Dopamine plays a critical role in the olfactory adaptive learning pathway in Caenorhabditis elegans,” Journal of Neuroscience Research, vol. 100, no. 11, pp. 2028-2043, Nov 2022, doi: 10.1002/jnr.25112.

26. C. H. Rankin, C. D. Beck, and C. M. Chiba, “Caenorhabditis elegans: a new model system for the study of learning and memory,” Behav Brain Res, vol. 37, no. 1, pp. 89-92, Feb 12 1990, doi: 10.1016/0166-4328(90)90074-o.

27. Y. Wang et al., “Aesculin offers increased resistance against oxidative stress and protective effects against Abeta-induced neurotoxicity in Caenorhabditis elegans,” Eur J Pharmacol, vol. 917, p. 174755, Feb 15 2022, doi: 10.1016/j.ejphar.2022.174755.

28. C. I. Bargmann, “Chemosensation in C. elegans,” WormBook : the online review of C. elegans biology, pp. 1-29, Oct 25 2006, doi: 10.1895/wormbook.1.123.1.

29. M. S. Lopez-Meza, G. Otero-Ojeda, J. A. Estrada, F. J. Esquivel-Hernandez, and I. Contreras, “The impact of nutritive and non-nutritive sweeteners on the central nervous system: preliminary study,” Nutritional neuroscience, vol. 25, no. 8, pp. 1623-1632, Aug 2022, doi: 10.1080/1028415X.2021.1885239.

30. Erbas et al., “Evaluation of long-term effects of artificial sweeteners on rat brain: a biochemical, behavioral, and histological study,” Journal of biochemical and molecular toxicology, vol. 32, no. 6, p. e22053, Jun 2018, doi: 10.1002/jbt.22053.

31. Jiao Yan, “Using nematodes as a model to study the consumption safety of three commonly used sugar substitutes,” M.S., Jilin University, 2018.

32. M. Zhang et al., “Aspartame and sucralose extend the lifespan and improve the health status of C. elegans,” Food & function, vol. 12, no. 20, pp. 9912-9921, Oct 19 2021, doi: 10.1039/d1fo01579f.

33. N. F. Salaya-Velazquez, L. A. Lopez-Mucino, S. Mejia-Chavez, P. Sanchez-Aparicio, A. A. Dominguez-Guadarrama, and A. Venebra-Munoz, “Anandamide and sucralose change DeltaFosB expression in the reward system,” Neuroreport, vol. 31, no. 3, pp. 240-244, Feb 5 2020, doi: 10.1097/WNR.0000000000001400.

34. C. Salim, N. Thadathil, M. Muralidhara, and P. S. Rajini, “Insights on the age dependent neurodegeneration induced by Monocrotophos, (an organophosphorous insecticide) in Caenorhabditis elegans fed high glucose: Evidence in wild and transgenic strains,” Comparative biochemistry and physiology. Toxicology & pharmacology : CBP, vol. 211, pp. 15-24, Sep 2018, doi: 10.1016/j.cbpc.2018.05.002.

35. Lingli Zhang, “A study on the relationship and mechanism between dietary intake pattern and individual behavior,” PhD, Shanghai Jiao Tong University, 2019.

36. N. Guo, J. Wang, and X. Wang, “Effect of starvation and high-carbohydrate diet on learning ability of Caenorhabditis elegans,” Heliyon, vol. 5, no. 3, p. e01289, Mar 2019, doi: 10.1016/j.heliyon.2019.e01289.

37. V. Vukojevic et al., “A role for alpha-adducin (ADD-1) in nematode and human memory,” The EMBO journal, vol. 31, no. 6, pp. 1453-66, Mar 21 2012, doi: 10.1038/emboj.2012.14.

38. S. E. Swithers, “Artificial sweeteners produce the counterintuitive effect of inducing metabolic derangements,” Trends in endocrinology and metabolism: TEM, vol. 24, no. 9, pp. 431-41, Sep 2013, doi: 10.1016/j.tem.2013.05.005.

39. S. L. Casperson, L. Johnson, and J. N. Roemmich, “The relative reinforcing value of sweet versus savory snack foods after consumption of sugar- or non-nutritive sweetened beverages,” Appetite, vol. 112, pp. 143-149, May 1 2017, doi: 10.1016/j.appet.2017.01.028.

40. L. Tsan et al., “Early-life low-calorie sweetener consumption disrupts glucose regulation, sugar-motivated behavior, and memory function in rats,” JCI insight, vol. 7, no. 20, Oct 24 2022, doi: 10.1172/jci.insight.157714.

41. R. E. Perszyk et al., “GluN2D-Containing N-methyl-d-Aspartate Receptors Mediate Synaptic Transmission in Hippocampal Interneurons and Regulate Interneuron Activity,” Molecular pharmacology, vol. 90, no. 6, pp. 689-702, Dec 2016, doi: 10.1124/mol.116.105130.

42. P. R. Zoladz et al., “ADRA2B deletion variant influences time-dependent effects of pre-learning stress on long-term memory,” Neurobiology of learning and memory, vol. 140, pp. 71-81, Apr 2017, doi: 10.1016/j.nlm.2017.02.014.

43. P. R. Zoladz et al., “ADRA2B deletion variant selectively predicts stress-induced enhancement of long-term memory in females,” Psychoneuroendocrinology, vol. 48, pp. 111-22, Oct 2014, doi: 10.1016/j.psyneuen.2014.06.012.

44. C. Miller, J. Dono, M. Scully, B. Morley, and K. Ettridge, “Adolescents’ knowledge and beliefs regarding health risks of soda and diet soda consumption,” Public health nutrition, vol. 25, no. 11, pp. 3044-3053, Nov 2022, doi: 10.1017/S1368980022001719.

Data Availability

The datasets used and/or analyzed during the current study will be available from the authors upon reasonable request.

This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License. Authors who publish this series agree to the following terms:

1. Authors retain copyright and grant the series right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgment of the work's authorship and initial publication in this series.

2. Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the series's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgment of its initial publication in this series.

3. Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See Open Access Instruction).

Volume Title
Proceedings of the 2nd International Conference on Modern Medicine and Global Health
ISBN (Print)
978-1-83558-195-7
ISBN (Online)
978-1-83558-196-4
Published Date
04 December 2023
Series
Theoretical and Natural Science
ISSN (Print)
2753-8818
ISSN (Online)
2753-8826
DOI
10.54254/2753-8818/16/20240509
Copyright
04 December 2023
Open Access
This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

Copyright © 2023 EWA Publishing. Unless Otherwise Stated