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Nutritional Neuroscience
An International Journal on Nutrition, Diet and Nervous System
Volume 21, 2018 - Issue 5
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Neurophysiological symptoms and aspartame: What is the connection?

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References

  • Rowe RC, Sheskey PJ, Quinn M. Handbook of pharmaceutical excipients – 7th edition. Pharm Dev Technol. 2013;18:544. doi: 10.3109/10837450.2012.751408
  • Nofre C, Tinti JM. Neotame: discovery, properties, utility. Food Chem. 2000;69(3):245–57. doi: 10.1016/S0308-8146(99)00254-X
  • Magnuson B. Aspartame-facts and fiction. NZ Med J. 2010;123(1311):53–7.
  • Renwick A, Nordmann H. First European conference on aspartame: putting safety and benefits into perspective. Synopsis of presentations and conclusions. Food Chem Toxicol. 2007;45(7):1308–13. doi: 10.1016/j.fct.2007.02.019
  • Food U, Administration D. Artificial sweeteners: no calories… sweet. FDA Consumer Magazine. 2006;40:27–28.
  • Lindseth GN, Coolahan SE, Petros TV, Lindseth PD. Neurobehavioral effects of aspartame consumption. Res Nurs Health. 2014;37(3):185–93. doi: 10.1002/nur.21595
  • Rycerz K, Jaworska-Adamu JE. Effects of aspartame metabolites on astrocytes and neurons. Folia Neuropathol. 2013;51(1):10–17. doi: 10.5114/fn.2013.34191
  • Humphries P, Pretorius E, Naude H. Direct and indirect cellular effects of aspartame on the brain. Eur J Clin Nutr. 2008;62(4):451–62. doi: 10.1038/sj.ejcn.1602866
  • Chattopadhyay S, Raychaudhuri U, Chakraborty R. Artificial sweeteners – a review. J Food Sci Technol. 2014;51(4):611–21. doi: 10.1007/s13197-011-0571-1
  • Abbott NJ, Rönnbäck L, Hansson E. Astrocyte–endothelial interactions at the blood–brain barrier. Nat Rev Neurosci. 2006;7(1):41–53. doi: 10.1038/nrn1824
  • Millan MJ, Agid Y, Brüne M, Bullmore ET, Carter CS, Clayton NS, et al. Cognitive dysfunction in psychiatric disorders: characteristics, causes and the quest for improved therapy. Nat Rev Drug Discov. 2012;11(2):141–68. doi: 10.1038/nrd3628
  • Maher TJ, Wurtman RJ. Possible neurologic effects of aspartame, a widely used food additive. Environ Health Perspect. 1987;75:53. doi: 10.1289/ehp.877553
  • Wall KM, Pardridge WM. Decreases in brain protein synthesis elicited by moderate increases in plasma phenylalanine. Biochem Biophys Res Commun. 1990;168(3):1177–83. doi: 10.1016/0006-291X(90)91153-J
  • Mathew H, Darren M, Jason A, Melanie C, Kimberly S. Attention and reaction time in university students following the consumption of red bull®. Open Nutr J. 2009;3(1):8–10. doi: 10.2174/1874288200903010008
  • Harte C, Kanarek R. The effects of nicotine and sucrose on spatial memory and attention. Nutr Neurosci. 2004;7:121–5. doi: 10.1080/10284150410001704543
  • Sünram-Lea SI, Foster JK, Durlach P, Perez C. Investigation into the significance of task difficulty and divided allocation of resources on the glucose memory facilitation effect. Psychopharmacology. 2002;160(4):387–97. doi: 10.1007/s00213-001-0987-9
  • Konen J, Sia T, Czuchry M, Stuntz P, Bahr G, Barth T, et al., editors. Perceived memory impairment in aspartame users. Society for Neuroscience 30th Annual Meeting, New Orleans, LA; 2000.
  • Shaywitz BA, Sullivan CM, Anderson GM, Gillespie SM, Sullivan B, Shaywitz SE. Aspartame, behavior, and cognitive function in children with attention deficit disorder. Pediatrics. 1994;93(1):70–75.
  • Wolraich ML, Lindgren SD, Stumbo PJ, Stegink LD, Appelbaum MI, Kiritsy MC. Effects of diets high in sucrose or aspartame on the behavior and cognitive performance of children. N Engl J Med. 1994;330(5):301–7. doi: 10.1056/NEJM199402033300501
  • Ashok I, Sheeladevi R. Neurobehavioral changes and activation of neurodegenerative apoptosis on long-term consumption of aspartame in the rat brain. J Nutr Intermediary Metab. 2015;2(3):76–85. doi: 10.1016/j.jnim.2015.09.001
  • Ashok I, Sheeladevi R, Wankhar D. Effect of long-term aspartame (artificial sweetener) on anxiety, locomotor activity and emotionality behavior in Wistar Albino rats. Biomed Preventive Nutr. 2014;4(1):39–43. doi: 10.1016/j.bionut.2013.04.002
  • Collison KS, Makhoul NJ, Zaidi MZ, Saleh SM, Andres B, Inglis A, et al. Gender dimorphism in aspartame-induced impairment of spatial cognition and insulin sensitivity. PLoS One. 2012;7(4):e31570. doi: 10.1371/journal.pone.0031570
  • Kim JY, Seo J, Cho KH. Aspartame-fed zebrafish exhibit acute deaths with swimming defects and saccharin-fed zebrafish have elevation of cholesteryl ester transfer protein activity in hypercholesterolemia. Food Chem Toxicol. 2011;49(11):2899–905. doi: 10.1016/j.fct.2011.08.001
  • Christian B, McConnaughey K, Bethea E, Brantley S, Coffey A, Hammond L, et al. Chronic aspartame affects T-maze performance, brain cholinergic receptors and Na+, K+-ATPase in rats. Pharmacol Biochem Behav. 2004;78(1):121–7. doi: 10.1016/j.pbb.2004.02.017
  • Park CH, Choi SH, Piao Y, Kim S-H, Lee Y-J, Kim H-S, et al. Glutamate and aspartate impair memory retention and damage hypothalamic neurons in adult mice. Toxicol Lett. 2000;115(2):117–25. doi: 10.1016/S0378-4274(00)00188-0
  • Wurtman RJ. Neurochemical changes following high-dose aspartame with dietary carbohydrates [letter]. New England Journal of Medicine (USA). 1983.
  • Glushakov A, Dennis D, Sumners C, Seubert C, Martynyuk A. L-phenylalanine selectively depresses currents at glutamatergic excitatory synapses. J Neurosci Res. 2003;72(1):116–24. doi: 10.1002/jnr.10569
  • Koe BK, Weissman A. p-Chlorophenylalanine: a specific depletor of brain serotonin. J Pharmacol Exp Ther. 1966;154(3):499–516.
  • McKean CM. The effects of high phenylalanine concentrations on serotinin and catecholamine metabolism in the human brain. Brain Res. 1972;47(2):469–76. doi: 10.1016/0006-8993(72)90653-1
  • Maletic-Savatic M, Malinow R, Svoboda K. Rapid dendritic morphogenesis in CA1 hippocampal dendrites induced by synaptic activity. Science. 1999;283(5409):1923–7. doi: 10.1126/science.283.5409.1923
  • Fischer M, Kaech S, Wagner U, Brinkhaus H, Matus A. Glutamate receptors regulate actin-based plasticity in dendritic spines. Nat Neurosci. 2000;3(9):887–94. doi: 10.1038/78791
  • Borroni AM, Fichtenholtz H, Woodside BL, Teyler TJ. Role of voltage-dependent calcium channel long-term potentiation (LTP) and NMDA LTP in spatial memory. J Neurosci. 2000;20(24):9272–6.
  • Rondi-Reig L, Libbey M, Eichenbaum H, Tonegawa S. CA1-specific N-methyl-d-aspartate receptor knockout mice are deficient in solving a nonspatial transverse patterning task. Proc Natl Acad Sci. 2001;98(6):3543–8. doi: 10.1073/pnas.041620798
  • Ikeda M. Hydroxylation of phenylalanine by purified preparations of adrenal and brain tyrosine hydroxylase. Biochem Biophys Res Commun. 1965;18(4):482–8. doi: 10.1016/0006-291X(65)90778-3
  • Shiman R, Akino M, Kaufman S. Solubilization and partial purification of tyrosine hydroxylase from bovine adrenal medulla. J Biol Chem. 1971;246(5):1330–40.
  • Brozoski TJ, Brown RM, Rosvold H, Goldman PS. Cognitive deficit caused by regional depletion of dopamine in prefrontal cortex of rhesus monkey. Science. 1979;205(4409):929–32. doi: 10.1126/science.112679
  • Lange KW, Robbins T, Marsden C, James M, Owen A, Paul G. l-Dopa withdrawal in Parkinson's disease selectively impairs cognitive performance in tests sensitive to frontal lobe dysfunction. Psychopharmacology. 1992;107(2–3):394–404. doi: 10.1007/BF02245167
  • Georgieff MK. Nutrition and the developing brain: nutrient priorities and measurement. Am J Clin Nutr. 2007;85(2):614S–20S.
  • Matalon R, Surendran S, Matalon KM, Tyring S, Quast M, Jinga W, et al. Future role of large neutral amino acids in transport of phenylalanine into the brain. Pediatrics. 2003;112(Supplement 4):1570–4.
  • Azmitia EC. Modern views on an ancient chemical: serotonin effects on cell proliferation, maturation, and apoptosis. Brain Res Bull. 2001;56(5):413–24. doi: 10.1016/S0361-9230(01)00614-1
  • Buhot M-C. Serotonin receptors in cognitive behaviors. Curr Opin Neurobiol. 1997;7(2):243–54. doi: 10.1016/S0959-4388(97)80013-X
  • Davidson RJ, Putnam KM, Larson CL. Dysfunction in the neural circuitry of emotion regulation – a possible prelude to violence. Science. 2000;289(5479):591–4. doi: 10.1126/science.289.5479.591
  • Yuen EY, Jiang Q, Chen P, Gu Z, Feng J, Yan Z. Serotonin 5-HT1A receptors regulate NMDA receptor channels through a microtubule-dependent mechanism. J Neurosci. 2005;25(23):5488–501. doi: 10.1523/JNEUROSCI.1187-05.2005
  • Luciana M, Burgund ED, Berman M, Hanson KL. Effects of tryptophan loading on verbal, spatial and affective working memory functions in healthy adults. J Psychopharmacol. 2001;15(4):219–30. doi: 10.1177/026988110101500410
  • Park S, Coull J, McShane R, Young A, Sahakian B, Robbins T, et al. Tryptophan depletion in normal volunteers produces selective impairments in learning and memory. Neuropharmacology. 1994;33(3):575–88. doi: 10.1016/0028-3908(94)90089-2
  • Schmitt J, Wingen M, Ramaekers J, Evers E, Riedel W. Serotonin and human cognitive performance. Curr Pharm Des. 2006;12(20):2473–86. doi: 10.2174/138161206777698909
  • Buhot M-C, Martin S, Segu L. Role of serotonin in memory impairment. Annal Med. 2000;32(3):210–21. doi: 10.3109/07853890008998828
  • Dingledine R, Borges K, Bowie D, Traynelis SF. The glutamate receptor ion channels. Pharmacol Rev. 1999;51(1):7–62.
  • Curtis D, Phillis J, Watkins J. The chemical excitation of spinal neurons by certain acidic amino acids. J Physiol. 1960;150(3):656–82. doi: 10.1113/jphysiol.1960.sp006410
  • Robinson MB, Coyle J. Glutamate and related acidic excitatory neurotransmitters: from basic science to clinical application. FASEB J. 1987;1(6):446–55. doi: 10.1096/fasebj.1.6.2890549
  • Kessler M, Terramani T, Lynch G, Baudry M. A glycine site associated with N-methyl-d-aspartic acid receptors: characterization and identification of a new class of antagonists. J Neurochem. 1989;52(4):1319–28. doi: 10.1111/j.1471-4159.1989.tb01881.x
  • MacDonald JF, Jackson MF, Beazely MA. Hippocampal long-term synaptic plasticity and signal amplification of NMDA receptors. Crit Rev Neurobiol. 2006;18(1–2):71–84. doi: 10.1615/CritRevNeurobiol.v18.i1-2.80
  • Errico F, Nisticò R, Palma G, Federici M, Affuso A, Brilli E, et al. Increased levels of d-aspartate in the hippocampus enhance LTP but do not facilitate cognitive flexibility. Mol Cell Neurosci. 2008;37(2):236–46. doi: 10.1016/j.mcn.2007.09.012
  • Cui B, Wu M, She X, Liu H. Impulse noise exposure in rats causes cognitive deficits and changes in hippocampal neurotransmitter signaling and tau phosphorylation. Brain Res. 2012;1427:35–43. doi: 10.1016/j.brainres.2011.08.035
  • Jacobson L, Sapolsky R. The role of the hippocampus in feedback regulation of the hypothalamic-pituitary-adrenocortical axis. Endocr Rev. 1991;12(2):118–34. doi: 10.1210/edrv-12-2-118
  • Kuningas M, De Rijk RH, Westendorp RG, Jolles J, Slagboom PE, Van Heemst D. Mental performance in old age dependent on cortisol and genetic variance in the mineralocorticoid and glucocorticoid receptors. Neuropsychopharmacology. 2007;32(6):1295–301. doi: 10.1038/sj.npp.1301260
  • Lupien SJ, Maheu F, Tu M, Fiocco A, Schramek TE. The effects of stress and stress hormones on human cognition: implications for the field of brain and cognition. Brain Cogn. 2007;65(3):209–37. doi: 10.1016/j.bandc.2007.02.007
  • Choudhary AK, Devi RS. Imbalance of the oxidant-antioxidant status by aspartame in the organs of immune system of Wistar albino rats. Afr J Pharm Pharmacol. 2014;8:220–30. doi: 10.5897/AJPP2013.3838
  • Iyyaswamy A, Rathinasamy S. Effect of chronic exposure to aspartame on oxidative stress in brain discrete regions of albino rats. J Biosci. 2012;37(4):679–88. doi: 10.1007/s12038-012-9236-0
  • Coyle JT, Puttfarcken P. Oxidative stress, glutamate, and neurodegenerative disorders. Science. 1993;262(5134):689–95. doi: 10.1126/science.7901908
  • Abdel-Salam OM, Salem NA, Hussein JS. Effect of aspartame on oxidative stress and monoamine neurotransmitter levels in lipopolysaccharide-treated mice. Neurotoxic Res. 2012;21(3):245–55. doi: 10.1007/s12640-011-9264-9
  • Abhilash M, Sauganth Paul M, Varghese MV, Nair RH. Long-term consumption of aspartame and brain antioxidant defense status. Drug Chem Toxicol. 2013;36(2):135–40. doi: 10.3109/01480545.2012.658403
  • Ashok I, Sheeladevi R. Biochemical responses and mitochondrial mediated activation of apoptosis on long-term effect of aspartame in rat brain. Redox Biol. 2014;2:820–31. doi: 10.1016/j.redox.2014.04.011
  • Choudhary AK, Sundareswaran L, Devi RS. Effects of aspartame on the evaluation of electrophysiological responses in Wistar albino rats. J Taibah Univ Sci. 2016;10(4):505–12. doi: 10.1016/j.jtusci.2015.07.006
  • Avshalumov MV, Chen BT, Rice ME. Mechanisms underlying H2O2-mediated inhibition of synaptic transmission in rat hippocampal slices. Brain Res. 2000;882(1):86–94. doi: 10.1016/S0006-8993(00)02835-3
  • Cowen P, Sherwood AC. The role of serotonin in cognitive function: evidence from recent studies and implications for understanding depression. J Psychopharmacol. 2013;27(7):575–83. doi: 10.1177/0269881113482531
  • McDermott LM, Ebmeier KP. A meta-analysis of depression severity and cognitive function. J Affective Disord. 2009;119(1):1–8. doi: 10.1016/j.jad.2009.04.022
  • Laird JE. Extending the soar cognitive architecture. Front Artif Intell Appl. 2008;171:224.
  • Wright WF, Bower GH. Mood effects on subjective probability assessment. Organizational Behav Human Decis Processes. 1992;52(2):276–91. doi: 10.1016/0749-5978(92)90039-A
  • Booij L, Van der Does AW, Haffmans PJ, Riedel WJ, Fekkes D, Blom MJ. The effects of high-dose and low-dose tryptophan depletion on mood and cognitive functions of remitted depressed patients. J Psychopharmacol. 2005;19(3):267–75. doi: 10.1177/0269881105051538
  • Barnes NM, Sharp T. A review of central 5-HT receptors and their function. Neuropharmacology. 1999;38(8):1083–152. doi: 10.1016/S0028-3908(99)00010-6
  • Meneses A. 5-HT system and cognition. Neurosci Biobehav Rev. 1999;23(8):1111–25. doi: 10.1016/S0149-7634(99)00067-6
  • Bhagwagar Z, Cowen PJ, Goodwin GM, Harmer CJ. Normalization of enhanced fear recognition by acute SSRI treatment in subjects with a previous history of depression. Am J Psychiatry. 2004;161(1):166–8. doi: 10.1176/appi.ajp.161.1.166
  • Smith KA, Morris JS, Friston KJ, Cowen PJ, Dolan RJ. Brain mechanisms associated with depressive relapse and associated cognitive impairment following acute tryptophan depletion. Br J Psychiatry. 1999;174(6):525–9. doi: 10.1192/bjp.174.6.525
  • Walton RG, Hudak R, Green-Waite RJ. Adverse reactions to aspartame: double-blind challenge in patients from a vulnerable population. Biol Psychiatry. 1993;34(1–2):13–17. doi: 10.1016/0006-3223(93)90251-8
  • Reid M, Hammersley R, Duffy M. Effects of sucrose drinks on macronutrient intake, body weight, and mood state in overweight women over 4 weeks. Appetite. 2010;55(1):130–6. doi: 10.1016/j.appet.2010.05.001
  • Reid M, Hammersley R. The effects of blind substitution of aspartame-sweetened for sugar-sweetened soft drinks on appetite and mood. Br Food J. 1998;100(5):254–9. doi: 10.1108/00070709810221508
  • Pivonka E, Grunewald K. Aspartame-or sugar-sweetened beverages: effects on mood in young women. J Am Dietetic Assoc. 1990;90(2):250–4.
  • Saravis S, Schachar R, Zlotkin S, Leiter LA, Anderson GH. Aspartame: effects on learning, behavior, and mood. Pediatrics. 1990;86(1):75–83.
  • Lieberman HR, Caballero B, Emde GG, Bernstein JG. The effects of aspartame on human mood, performance, and plasma amino acid levels. Dietary phenylalanine and brain function. Birkhäuser Boston: Springer; 1988. p. 196–200.
  • Ryan-Harshman M, Leiter LA, Anderson GH. Phenylalanine and aspartame fail to alter feeding behavior, mood and arousal in men. Physiol Behav. 1987;39(2):247–53. doi: 10.1016/0031-9384(87)90017-5
  • Goerss AL, Wagner GC, Hill WL. Acute effects of aspartame on aggression and neurochemistry of rats. Life Sci. 2000;67(11):1325–9. doi: 10.1016/S0024-3205(00)00723-2
  • LaBuda CJ, Hale RL. Anxiety in mice following acute aspartame and ethanol exposure. Alcohol. 2000;20(1):69–74. doi: 10.1016/S0741-8329(99)00060-9
  • Roberts H. Pseudotumor cerebri due to aspartame disease. Townsend Letter for doctors and patients. 2002:66–9.
  • Johns DR. Migraine provoked by aspartame. N Engl J Med. 1986;315(7):456.
  • Koehler SM, Glaros A. The effect of aspartame on migraine headache. Headache J Head Face Pain. 1988;28(1):10–4. doi: 10.1111/j.1365-2524.1988.hed2801010.x
  • Lipton R, Newman L, Solomon S, Steinmetzer R, Kunkel R, Elsas L, et al. Aspartame and headache. N Engl J Med. 1988;318:1200. doi: 10.1056/NEJM198805053181812
  • Lipton RB, Newman LC, Cohen JS, Solomon S. Aspartame as a dietary trigger of headache. Headache J Head Face Pain. 1989;29(2):90–2. doi: 10.1111/j.1526-4610.1989.hed2902090.x
  • Newman LC, Lipton RB. Migraine MLT-Down: an unusual presentation of migraine in patients with aspartame-triggered headaches. Headache J Head Face Pain. 2001;41(9):899–901. doi: 10.1046/j.1526-4610.2001.01164.x
  • Van den Eeden S, Koepsell TD, Longstreth W, Van Belle G, Daling J, McKnight B. Aspartame ingestion and headaches: a randomized crossover trial. Neurology. 1994;44(10):1787. doi: 10.1212/WNL.44.10.1787
  • Schiffman SS, Buckley III CE, Sampson H, Massey E, Baraniuk J, Follett J, et al. Aspartame and susceptibility to headache. N Engl J Med. 1987;317(19):1181–5. doi: 10.1056/NEJM198711053171903
  • Borkum JM. Migraine triggers and oxidative stress: a narrative review and synthesis. Headache J Head Face Pain. 2016;56(1):12–35. doi: 10.1111/head.12725
  • Abdel-Salam O, Salem N, El-Shamarka M, Hussein J, Ahmed N, El-Nagar M. Studies on the effects of aspartame on memory and oxidative stress in brain of mice. Eur Rev Med Pharmacol Sci. 2012;16(15):2092–101.
  • Humphrey P, Feniuk W, Perren MJ, Beresford IJ, Skingle M, Whalley ET. Serotonin and migraine. Annal NY Acad Sci. 1990;600(1):587–98. doi: 10.1111/j.1749-6632.1990.tb16912.x
  • Tephly TR. The toxicity of methanol. Life Sci. 1991;48(11):1031–41. doi: 10.1016/0024-3205(91)90504-5
  • Garthwaite J. Glutamate, nitric oxide and cell-cell signalling in the nervous system. Trends Neurosci. 1991;14(2):60–67. doi: 10.1016/0166-2236(91)90022-M
  • Pietrobon D, Striessnig J. Neurobiology of migraine. Nat Rev Neurosci. 2003;4(5):386–98. doi: 10.1038/nrn1102
  • Bartsch T, Goadsby P. Increased responses in trigeminocervical nociceptive neurons to cervical input after stimulation of the dura mater. Brain. 2003;126(8):1801–13. doi: 10.1093/brain/awg190
  • Hamel E. Serotonin and migraine: biology and clinical implications. Cephalalgia. 2007;27(11):1293–300. doi: 10.1111/j.1468-2982.2007.01476.x
  • Walton RG. The possible role of aspartame in seizure induction. Dietary phenylalanine and brain function. Birkhäuser Boston: Springer; 1988. p. 159–62.
  • McCall RB. Effects of putative neurotransmitters on sympathetic preganglionic neurons. Annu Rev Physiol. 1988;50(1):553–64. doi: 10.1146/annurev.ph.50.030188.003005
  • Pinto JM, Maher TJ. Administration of aspartame potentiates pentylenetetrazole-and fluorothyl-induced seizures in mice. Neuropharmacology. 1988;27(1):51–55. doi: 10.1016/0028-3908(88)90200-6
  • Dailey J, Lasley SM, Burger R, Bettendorf A, Mishra P, Jobe P. Amino acids, monoamines and audiogenic seizures in genetically epilepsy-prone rats: effects of aspartame. Epilepsy Res. 1991;8(2):122–33. doi: 10.1016/0920-1211(91)90080-Y
  • Rowan AJ, Shaywitz BA, Tuchman L, French JA, Luciano D, Sullivan CM. Aspartame and seizure susceptibility: results of a clinical study in reportedly sensitive individuals. Epilepsia. 1995;36(3):270–5. doi: 10.1111/j.1528-1157.1995.tb00995.x
  • Shaywitz B, Anderson G, Novotny E, Ebersole J, Sullivan C, Gillespie S. Aspartame has no effect on seizures or epileptiform discharges in epileptic children. Annal Neurol. 1994;35(1):98–103. doi: 10.1002/ana.410350115
  • Camfield P, Camfield C, Dooley J, Gordon K, Jollymore S, Weaver D. Aspartame exacerbates EEG spike-wave discharge in children with generalized absence epilepsy: a double-blind controlled study. Neurology. 1992;42(5):1000. doi: 10.1212/WNL.42.5.1000
  • Spiegel K, Leproult R, Van Cauter E. Impact of sleep debt on metabolic and endocrine function. Lancet. 1999;354(9188):1435–9. doi: 10.1016/S0140-6736(99)01376-8
  • Choudhary AK, Sundareswaran L, Devi RS. Effects of aspartame on the evaluation of electrophysiological responses in Wistar albino rats. J Taibah Univ Sci. 2016;10:505–12. doi: 10.1016/j.jtusci.2015.07.006
  • Flacker JM, Lipsitz LA. Neural mechanisms of delirium: current hypotheses and evolving concepts. J Gerontol Series A: Biol Sci Med Sci. 1999;54(6):B239–46. doi: 10.1093/gerona/54.6.B239
  • Woodbury DM, Timiras PS, Vernadakis A. Influence of adrenocortical steroids on brain function and metabolism. In: Hoagland H, (eds.) Hormones, brain function, and behavior. New York: Academic Press, 1957. p. 27. doi: 10.1016/B978-0-12-395494-7.50006-3
  • Tsigos C, Chrousos GP. Hypothalamic–pituitary–adrenal axis, neuroendocrine factors and stress. J Psychosomatic Res. 2002;53(4):865–71. doi: 10.1016/S0022-3999(02)00429-4
  • Leproult R, Van Cauter E. Role of sleep and sleep loss in hormonal release and metabolism. Pediatric Neuroendocrinology. 17. Basel: Karger Publishers; 2009. p. 11–21.
  • Adrien J. Neurobiological bases for the relation between sleep and depression. Sleep Med Rev. 2002;6(5):341–51. doi: 10.1053/smrv.2001.0200
  • Otzenberger H, Gronfier C, Simon C, Charloux A, Ehrhart J, Piquard F, et al. Dynamic heart rate variability: a tool for exploring sympathovagal balance continuously during sleep in men. Am J Physiol-Heart Circulatory Physiol. 1998;275(3):H946–H50. doi: 10.1152/ajpheart.1998.275.3.H946
  • Tilson HA, Hong J, Sobotka TJ. High doses of aspartame have no effects on sensorimotor function or learning and memory in rats. Neurotoxicol Teratol. 1991;13(1):27–35. doi: 10.1016/0892-0362(91)90024-Q
  • Choudhary AK, Sheeladevi R. Effect of aspartame in spinal cord and motor behavior in Wistar albino rats. J Behav Health. 2014;3(2):107–11. doi: 10.5455/jbh.20140606114825

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