Nutrition
Volume 27, Issue 1 , Pages 81-85 , January 2011

Neonatal exposure to sucralose does not alter biochemical markers of neuronal development or adult behavior

Received 2 July 2009 ,Accepted 21 October 2009.

References 

  1. Food and Drug Administration. Sucralose—a new artificial sweetener. Med Lett Drugs Ther. 1998;40(1030):67–68
  2. Food and Drug Administration. Food additives permitted for direct addition to food for human consumption: sucralose. 21CFR17263. 1998;
  3. Food and Drug Administration. Food additives permitted for direct addition to food for human consumption: sucralose. 21CFR17264. 1999;
  4. Food and Drug Administration. Artificial sweeteners: no calories.sweet!. FDA Consumer Mag. 2006;40:27–28
  5. Grotz VL. Sucralose and migraine. Headache. 2008;48(1):164–165
  6. John BA, Wood SG, Hawkins DR. The pharmacokinetics and metabolism of sucralose in the mouse. Food Chem Toxicol. 2000;38(suppl 2):S107–S110
  7. John BA, Wood SG, Hawkins DR. The pharmacokinetics and metabolism of sucralose in the rabbit. Food Chem Toxicol. 2000;38(suppl 2):S111–S113
  8. Wood SG, John BA, Hawkins DR. The pharmacokinetics and metabolism of sucralose in the dog. Food Chem Toxicol. 2000;38(suppl 2):S99–106
  9. Sims J, Roberts A, Daniel JW, Renwick AG. The metabolic fate of sucralose in rats. Food Chem Toxicol. 2000;38(suppl 2):S115–S121
  10. Mann SW, Yuschak MM, Amyes SJ, Aughton P, Finn JP. A combined chronic toxicity/carcinogenicity study of sucralose in Sprague-Dawley rats. Food Chem Toxicol. 2000;38(suppl 2):S71–S89
  11. Grice HC, Goldsmith LA. Sucralose—an overview of the toxicity data. Food Chem Toxicol. 2000;38(suppl 2):S1–S6
  12. Roberts A, Renwick AG, Sims J, Snodin DJ. Sucralose metabolism and pharmacokinetics in man. Food Chem Toxicol. 2000;38(suppl 2):S31–S41
  13. Lubick N. Artificial sweetener persists in the environment. Environ Sci Technol. 2008;42(9):3125
  14. Brorström-Lundén E, Svensson A, Viktor T, Woldegiorgis A, Remberger M, Kaj L, et al. Measurements of Sucralose in the Swedish Screening Program 2007, Part I; Sucralose in surface waters and STP samples. IVL Swedish Environmental Research Institute, 2007.
  15. Renwick AG. The intake of intense sweeteners—an update review. Food Addit Contam. 2006;23(4):327–338
  16. Davison AN, Dobbing J. Applied neurochemistry. Oxford: Blackwell; 1968;p. 178–221, 253–316
  17. Dobbing J, Sands J. Comparative aspects of the brain growth spurt. Early Hum Dev. 1979;3(1):79–83
  18. Johansson N, Eriksson P, Viberg H. Neonatal exposure to PFOS and PFOA in mice results in changes in proteins which are important for neuronal growth and synaptogenesis in the developing brain. Toxicol Sci. 2009;108(2):412–418
  19. Viberg H. Neonatal ontogeny and neurotoxic effect of decabrominated diphenyl ether (PBDE 209) on levels of synaptophysin and tau. Int J Dev Neurosci. 2009;27(5):423–429
  20. Viberg H. Exposure to polybrominated diphenyl ethers 203 and 206 during the neonatal brain growth spurt affects proteins important for normal neurodevelopment in mice. Toxicol Sci. 2009;109(2):306–311
  21. Viberg H, Mundy W, Eriksson P. Neonatal exposure to decabrominated diphenyl ether (PBDE 209) results in changes in BDNF, CaMKII and GAP-43, biochemical substrates of neuronal survival, growth, and synaptogenesis. Neurotoxicology. 2008;29(1):152–159
  22. Viberg H, Ponten E, Eriksson P, Gordh T, Fredriksson A. Neonatal ketamine exposure results in changes in biochemical substrates of neuronal growth and synaptogenesis, and alters adult behavior irreversibly. Toxicology. 2008;249(2–3):153–159
  23. Eriksson P, Jakobsson E, Fredriksson A. Brominated flame retardants: a novel class of developmental neurotoxicants in our environment?. Environ Health Perspect. 2001;109(9):903–908
  24. Johansson N, Fredriksson A, Eriksson P. Neonatal exposure to perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) causes neurobehavioural defects in adult mice. Neurotoxicology. 2008;29(1):160–169
  25. Viberg H, Fredriksson A, Jakobsson E, Orn U, Eriksson P. Neurobehavioral derangements in adult mice receiving decabrominated diphenyl ether (PBDE 209) during a defined period of neonatal brain development. Toxicol Sci. 2003;76(1):112–120
  26. Erondu NE, Kennedy MB. Regional distribution of type II Ca2+/calmodulin-dependent protein kinase in rat brain. J Neurosci. 1985;5(12):3270–3277
  27. Frankland PW, O'Brien C, Ohno M, Kirkwood A, Silva AJ. Alpha-CaMKII–dependent plasticity in the cortex is required for permanent memory. Nature. 2001;411(6835):309–313
  28. Oestreicher AB, De Graan PN, Gispen WH, Verhaagen J, Schrama LH. B-50, the growth associated protein-43: modulation of cell morphology and communication in the nervous system. Prog Neurobiol. 1997;53(6):627–686
  29. Rongo C, Kaplan JM. CaMKII regulates the density of central glutamatergic synapses in vivo. Nature. 1999;402(6758):195–199
  30. Sarnat HB, Born DE. Synaptophysin immunocytochemistry with thermal intensification: a marker of terminal axonal maturation in the human fetal nervous system. Brain Dev. 1999;21(1):41–50
  31. Valtorta F, Pennuto M, Bonanomi D, Benfenati F. Synaptophysin: leading actor or walk-on role in synaptic vesicle exocytosis?. Bioessays. 2004;26(4):445–453
  32. Wang JZ, Liu F. Microtubule-associated protein tau in development, degeneration and protection of neurons. Prog Neurobiol. 2008;85(2):148–175
  33. Viberg H. Neonatal ontogeny and neurotoxic effect of decabrominated diphenyl ether (PBDE 209) on levels of synaptophysin and tau. Int J Dev Neurosci. 2009;27(5):423–429
  34. Wilcoxon JS, Kuo AG, Disterhoft JF, Redei EE. Behavioral deficits associated with fetal alcohol exposure are reversed by prenatal thyroid hormone treatment: a role for maternal thyroid hormone deficiency in FAE. Mol Psychiatry. 2005;10(10):961–971
  35. Eriksson P, Ahlbom J, Fredriksson A. Exposure to DDT during a defined period in neonatal life induces permanent changes in brain muscarinic receptors and behaviour in adult mice. Brain Res. 1992;582(2):277–281
  36. Fredriksson A. MPTP-induced behavioural deficits in mice: validity and utility of a model of Parkinsonism (PhD thesis). Uppsala: Uppsala University; 1994;
  37. Kirk RE. Procedures for the behavioural science. Belmont, CA: Brooks/Cole; 1968;
  38. Eriksson P, Viberg H, Jakobsson E, Orn U, Fredriksson A. A brominated flame retardant, 2,2′,4,4′,5-pentabromodiphenyl ether: uptake, retention, and induction of neurobehavioral alterations in mice during a critical phase of neonatal brain development. Toxicol Sci. 2002;67(1):98–103
  39. Viberg H, Fredriksson A, Eriksson P. Neonatal exposure to polybrominated diphenyl ether (PBDE 153) disrupts spontaneous behaviour, impairs learning and memory, and decreases hippocampal cholinergic receptors in adult mice. Toxicol Appl Pharmacol. 2003;192(2):95–106
  40. Viberg H, Johansson N, Fredriksson A, Eriksson J, Marsh G, Eriksson P. Neonatal exposure to higher brominated diphenyl ethers, hepta-, octa-, or nonabromodiphenyl ether, impairs spontaneous behavior and learning and memory functions of adult mice. Toxicol Sci. 2006;92(1):211–218
  41. Jenner MR, Smithson A. Physicochemical properties of the sweetener sucralose. J Food Sci. 1989;54(6):1646–1649
  42. O'Callaghan JP, Miller DB. Acute exposure of the neonatal rat to triethyltin results in persistent changes in neurotypic and gliotypic proteins. J Pharmacol Exp Ther. 1988;244(1):368–378
  43. O'Callaghan JP, Miller DB. Acute exposure of the neonatal rat to tributyltin results in decreases in biochemical indicators of synaptogenesis and myelinogenesis. J Pharmacol Exp Ther. 1988;246(1):394–402
  44. Fujita M, Kadota T, Sato T. Developmental profiles of synaptophysin in granule cells of rat cerebellum: an immunohistocytochemical study. J Electron Microsc (Tokyo). 1996;45(3):185–194
  45. Dingemans MM, Ramakers GM, Gardoni F, van Kleef RG, Bergman A, Di Luca M, et al. Neonatal exposure to brominated flame retardant BDE-47 reduces long-term potentiation and postsynaptic protein levels in mouse hippocampus. Environ Health Perspect. 2007;115(6):865–870
  46. Kobayashi K, Tsuji R, Yoshioka T, Kushida M, Yabushita S, Sasaki M, et al. Effects of hypothyroidism induced by perinatal exposure to PTU on rat behavior and synaptic gene expression. Toxicology. 2005;212(2–3):135–147
  47. Daenen EW, Van der Heyden JA, Kruse CG, Wolterink G, Van Ree JM. Adaptation and habituation to an open field and responses to various stressful events in animals with neonatal lesions in the amygdala or ventral hippocampus. Brain Res. 2001;918(1–2):153–165
  48. Giovannini MG, Rakovska A, Benton RS, Pazzagli M, Bianchi L, Pepeu G. Effects of novelty and habituation on acetylcholine, GABA, and glutamate release from the frontal cortex and hippocampus of freely moving rats. Neuroscience. 2001;106(1):43–53

 This work was supported by grants from Formas, the Swedish Research Council for Environment, Agricultural Sciences and Spatial Planning.

PII: S0899-9007(09)00431-6

doi: 10.1016/j.nut.2009.10.007

Nutrition
Volume 27, Issue 1 , Pages 81-85 , January 2011