Effects of Treadmill Exercise and Tryptophan Supplementation on Antioxidant Level, Synaptic mRNA Expression, and Memory Function in High Fat Diet Aging Rats
Article Sidebar
Crossref Citations: 0
Main Article Content
Abstract
Introduction: Exercise training with antioxidant and anti-inflammatory supplements plays an effective role in dementia progression, and tryptophan is an essential amino acid that can be supplied through the diet. The present study aimed to investigate the effects of treadmill exercise and tryptophan supplementation on brain antioxidant levels, synapsin 1 (SYN1), brain-derived neurotrophic factor (BDNF), and postsynaptic density-95 (PSD-95) mRNA in rats fed a high‑fat diet (HFD).
Materials and methods: A total of 75 male rats, 2-3 months old, with an average weight of 527 grams, were randomly assigned to five groups, with five rats per group and three replicates. The first group was administered the standard low-fat diet daily (LF), the second group was administered the HFD daily (HF), the third group was administered the HFD along with a tryptophan supplement at 250 mg/kg/orally (HFTS), the fourth group was given the HFD along with the tryptophan supplement and exercised daily (HFETS), and the fifth group was fed the HFD only and exercised (HFE). Exercise training was performed on a rodent treadmill, three days/week for eight weeks. At the end of the exercise protocol and cognitive analyses (light/dark maze and Barnes maze), rats were euthanized, and brain tissue was collected for real-time polymerase chain reaction analysis of brain antioxidant, SYN1, BDNF, and PSD-95 mRNA.
Results: The HFD significantly raised serum total cholesterol and triglycerides compared to the low-fat diet, while the HFETS group reduced cholesterol to levels similar to the LF group. In the Barnes maze test, the HFETS group demonstrated the shortest escape time and fewest errors, indicating improved spatial learning, whereas no differences in anxiety-like behavior were observed in the light/dark maze analysis. Additionally, HFE and HFETS groups exhibited higher catalase levels and restored hippocampal PSD-95 expression, while SYN1 expression was increased in all HFD-fed groups compared to the LF group. BDNF expression did not differ significantly across all groups.
Conclusion: In aged rats, combining exercise with tryptophan supplementation partially mitigated HFD‑induced metabolic disturbances and improved spatial learning and memory. Exercise alone was more effective than tryptophan supplementation in preventing the adverse effects of an HDF during aging.
Article Details
This work is licensed under a Creative Commons Attribution 4.0 International License.
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors, and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.
References
Sainio EL, Pulkki K, and Young SN. L-Tryptophan: Biochemical, nutritional and pharmacological aspects. Amino acids. 1996; 10(1): 21-47. DOI: 10.1007/BF00806091
Fejes A, Párdutz Á, Toldi J, and Vécsei L. Kynurenine metabolites and migraine: Experimental studies and therapeutic perspectives. Curr Neuropharmacol. 2011; 9(2): 376-387. DOI: 10.2174/157015911795596621
Ito Y, Yonekura R, Nakagami Y, Maruta K, Koike T, Nagamura Y, et al. Tryptophan metabolism was accelerated by exercise in rat. In: Allegri G, Costa CVL, Ragazzi E, Steinhart H, and Varesio L, editors. Developments in tryptophan and serotonin metabolism. Advances in experimental medicine and biology. Boston, MA: Springer; 2003. p. 531-535. DOI: 10.1007/978-1-4615-0135-0_61
Notarangelo FM, Pocivavsek A, and Schwarcz R. Exercise your kynurenines to fight depression. Trends Neurosci. 2018; 41(8): 491-493. DOI: 10.1016/j.tins.2018.05.010
Richard DM, Dawes MA, Mathias CW, Acheson A, Hill-Kapturczak N, and Dougherty DM. L-Tryptophan: Basic metabolic functions, behavioral research and therapeutic indications. Int J Tryptophan Res. 2009; 2: 45-60. DOI: 10.4137/IJTR.S2129
Jenkins TA, Nguyen JCD, Polglaze KE, and Bertrand PP. Influence of tryptophan and serotonin on mood and cognition with a possible role of the gut-brain axis. Nutrients. 2016; 8(1): 56. DOI: 10.3390/nu8010056
Porter RJ, Lunn BS, and O'BRIEN JT. Effects of acute tryptophan depletion on cognitive function in Alzheimer's disease and in the healthy elderly. Psychol Med. 2003; 33(1): 41-49. DOI: 10.1017/S0033291702006906
Suzuki H, Yamashiro D, Ogawa S, Kobayashi M, Cho D, Iizuka A, et al. Intake of seven essential amino acids improves cognitive function and psychological and social function in middle-aged and older adults: A double-blind, randomized, placebo-controlled trial. Front Food Nutr Res. 2020; 7: 586166. DOI: 10.3389/fnut.2020.586166
Ghaheri S, Niapour A, Sakhaie N, Sadegzadeh F, and Saadati H. Postnatal depletion of serotonin affects the morphology of neurons and the function of the hippocampus in male rats. Int J Develop Neurosci. 2022; 82(3): 222-230. DOI: 10.1002/jdn.10174
Templeman JR, Thornton E, Cargo-Froom C, Squires EJ, Swanson KS, and Shoveller AK. Effects of incremental exercise and dietary tryptophan supplementation on the amino acid metabolism, serotonin status, stool quality, fecal metabolites, and body composition of mid-distance training sled dogs. J Anim Sci. 2020; 98(5): 1-12. DOI: 10.1093/jas/skaa128
Kashi A, Rezaei S, and Rafiee S. The effect of aerobic, aerobic in water and exercises in water on working memory in elderly women with Alzheimer's disease. J Gerontol Nurs. 2017; 3(3): 57-67. Available at: http://jgn.medilam.ac.ir/article-1-225-fa.html
Apryatin SA, Sidorova YS, Shipelin VA, Balakina A, Trusov NV, and Mazo VK. Neuromotor activity, anxiety and cognitive function in the in vivo model of alimentary hyperlipidemia and obesity. Bull Exp Biol Med. 2017; 163(1): 37-41. DOI: 10.1007/s10517-017-3732-z
Reynolds JC, Lai RW, Woodhead JST, Joly JH, Mitchell CJ, Cameron-Smith D, et al. MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis. Nat Commun. 2021; 12(1): 470. DOI: 10.1038/s41467-020-20790-0
Segal SK, Cotman CW, and Cahill LF. Exercise-induced noradrenergic activation enhances memory consolidation in both normal aging and patients with amnestic mild cognitive impairment. J Alzheimer's Dis. 2012; 32(4): 1011-1018. DOI: 10.3233/JAD-2012-121078
Ren H, Yu X, Yu L, Zhang Y, Xie H, Shi N, et al. Effects of different training loads on emotional state and mRNA and protein expressions of N-methyl-D-aspartate receptor subunits, postsynaptic density 95, and kinesin family member 17 in hippocampus of rats. Med Sci Monit. 2017; 23: 4954-4960. DOI: 10.12659/MSM.906781
Lee CC, Huang CC, Wu MY, and Hsu KS. Insulin stimulates postsynaptic density-95 protein translation via the phosphoinositide 3-kinase-Akt-mammalian target of rapamycin signaling pathway. J Biol Chem. 2005; 280(18): 18543-18550. DOI: 10.1074/jbc.M414112200
Coley AA, and Gao WJ. PSD95: A synaptic protein implicated in schizophrenia or autism? Prog Neuropsychopharmacol Biol Psychiatry. 2018; 82: 187-194. DOI: 10.1016/j.pnpbp.2017.11.016
Lisman J, Buzsáki G, Eichenbaum H, Nadel L, Ranganath C, and Redish AD. Viewpoints: How the hippocampus contributes to memory, navigation and cognition. Nat Neurosci. 2017; 20(11): 1434-1447. DOI: 10.1038/nn.4661
Ritchey M, Libby LA, and Ranganath C. Cortico-hippocampal systems involved in memory and cognition: The PMAT framework. Prog Brain Res. 2015; 219: 45-64. DOI: 10.1016/bs.pbr.2015.04.001
Mehrdad J, Leila E, and Emsehgol N. The effect of vitamin B12 on synaptic plasticity of hippocampus in Alzheimer's disease model rats. Int J Neurosci. 2023; 133(6): 654-659. DOI: 10.1080/00207454.2021.1962863
Shipelin VA, Trusov NV, Apryatin SA, Shumakova AA, Balakinaet AS, Riger NA, et al. Effects of tyrosine and tryptophan in rats with diet-induced obesity. Int J Mol Sci. 2021; 22(5): 2429. DOI: 10.3390/ijms22052429
Levin BE, and Dunn-Meynell AA. Defense of body weight depends on dietary composition and palatability in rats with diet induced obesity. Am J Physiol Regul Integr Comp Physiol. 2002; 282(1): R46–R54. DOI: 10.1152/ajpregu.2002.282.1.R46
Almeida SS, Tonkiss J, and Galler JR. Prenatal protein malnutrition affects exploratory behavior of female rats in the elevated plus-maze test. Physiol Behav. 1996; 60(2): 675-680. DOI: 10.1016/S0031-9384(96)80047-3
Hughes RN. The value of spontaneous alternation behavior (SAB) as a test of retention in pharmacological investigations of memory. Neurosci Biobehav Rev. 2004; 28(5): 497-505. DOI: 10.1016/j.neubiorev.2004.06.006
Li WY, Zhu QB, Jin LY, Yang Y, Xu XY, and Hu XY. Exosomes derived from human induced pluripotent stem cell-derived neural progenitor cells protect neuronal function under ischemic conditions. Neural Regen Res. 2021; 16(10): 2064-2070. DOI: 10.4103/1673-5374.308665
Salmi R, Presotto A, Scarry CJ, Hawman P, and Doran-Sheehy DM. Spatial cognition in western gorillas (Gorilla gorilla): An analysis of distance, linearity, and speed of travel routes. Anim Cogn. 2020; 23(3): 545-557. DOI: 10.1007/s10071-020-01358-3
Kanoski SE, and Davidson TL. Western diet consumption and cognitive impairment: Links to hippocampal dysfunction and obesity. Physiol Behav. 2011; 103(1): 59-68. DOI: 10.1016/j.physbeh.2010.12.003
Wu H, Liu Q, Kalavagunta PK, Huang Q, Lv W, An X, et al. Normal diet Vs High fat diet - A comparative study: Behavioral and neuroimmunological changes in adolescent male mice. Metab Brain Dis. 2018; 33(1): 177-190. DOI: 10.1007/s11011-017-0140-z
Ganji A, Salehi I, Nazari M, Taheri M, and Komaki A. Effects of Hypericum scabrum extract on learning and memory and oxidant/antioxidant status in rats fed a long-term high-fat diet. Metab Brain Dis. 2017; 32(4): 1255-1265. DOI: 10.1007/s11011-017-0022-4
de Souza RF, de Moraes SRA, Augusto RL, de Freitas Zanona A, Matos D, et al. Endurance training on rodent brain antioxidant capacity: A meta-analysis. Neurosci Res. 2019; 145: 1-9. DOI: 10.1016/j.neures.2018.09.002
Reiter RJ, Tan Dx, Cabrera J, and D'Arpa D. Melatonin and tryptophan derivatives as free radical scavengers and antioxidants. In: Huether G, Kochen W, Simat TJ, and Steinhart H, editors. Tryptophan, serotonin, and melatonin. Advances in experimental medicine and biology. Boston, MA: Springer; 1999. p. 379-387. DOI: 10.1007/978-1-4615-4709-9_48
Abbasnejad Z, Nasseri B, Zardooz H, and Ghasemi R. Time-course study of high fat diet induced alterations in spatial memory, hippocampal JNK, P38, ERK and Akt activity. Metab Brain Dis. 2019; 34(2): 659-673. DOI: 10.1007/s11011-018-0369-1
Ajayi AM, John KA, Emmanuel IB, Chidebe EO, and Adedapo ADA. High-fat diet-induced memory impairment and anxiety-like behavior in rats attenuated by peel extract of Ananas comosus fruit via atheroprotective, antioxidant and anti-inflammatory actions. Metab Open. 2021; 9: 100077. DOI: 10.1016/j.metop.2021.100077
Nelson AR, Sweeney MD, Sagare AP, and Zlokovic BV. Neurovascular dysfunction and neurodegeneration in dementia and Alzheimer's disease. Biochim Biophys Acta Mol Basis Dis. 2016; 1862(5): 887-900. DOI: 10.1016/j.bbadis.2015.12.016
Sattler FR. Growth hormone in the aging male. Best Pract Res Clin Endocrinol Metab. 2013; 27(4): 541-555. DOI: 10.1016/j.beem.2013.05.003
İSMAİL A, SELCEN A, AKIN B, İMRAN İA, AHMET A. Brain-derived neurotropic factor (BDNF) heterozygous mice are more susceptible to synaptic protein loss in cerebral cortex during high fat diet. Arch Biochem Physiol. 2017; 124: 442-447. DOI: 10.1080/13813455.2017.1420666
Madhu LN, Kodali M, Attaluri S, Shuai B, Melissari L, Rao X, et al. Melatonin improves brain function in a model of chronic Gulf War Illness with modulation of oxidative stress, NLRP3 inflammasomes, and BDNF-ERK-CREB pathway in the hippocampus. Redox Biol. 2021; 43: 101973. DOI: 10.1016/j.redox.2021.101973
Cheng MC, Lu CL, Luu SU, Tsai HM, Hsu SH, Chen TT, et al. Genetic and functional analysis of the DLG4 gene encoding the post-synaptic density protein 95 in schizophrenia. PLOS ONE. 2010; 5(12): e15107. DOI: 10.1371/journal.pone.0015107
Song SH, and Augustine GJ. Synapsin isoforms and synaptic vesicle trafficking. Mol Cells. 2015; 38(11): 936-940. DOI: 10.14348/molcells.2015.0233
Chio CC, Lin HJ, Tian YF, Chen YC, Lin MT, Lin CH, et al. Exercise attenuates neurological deficits by stimulating a critical HSP70/NF-κB/IL-6/synapsin I axis in traumatic brain injury rats. J Neuroinflammation. 2017; 14(1): 90. DOI: 10.1186/s12974-017-0867-9