Publication Cover
Nutritional Neuroscience
An International Journal on Nutrition, Diet and Nervous System
Volume 27, 2024 - Issue 6
347
Views
1
CrossRef citations to date
0
Altmetric
Research Article

Independent and combined effects of astaxanthin and omega-3 on behavioral deficits and molecular changes in a prenatal valproic acid model of autism in rats

, & ORCID Icon

References

  • Faras H, al Ateeqi N, Tidmarsh L. Autism spectrum disorders. Ann Saudi Med. 2010;30(4):295–300. doi:10.4103/0256-4947.65261.
  • Rapin I, Tuchman RF. Autism: definition, neurobiology, screening, diagnosis. Pediatr Clin N Am. 2008;55(5):1129–46. doi:10.1016/J.PCL.2008.07.005.
  • American Psychiatric Association. Diagnostic and statistical manual of mental disorders. Washington, DC: American Psychiatric Association Publishing; 2022. doi:10.1176/appi.books.9780890425787.
  • Centers for Disease Control and Prevention. (n.d.). [accessed 2023 Jan 2]. Available from: https://www.cdc.gov/.
  • World Health Organization (WHO). (n.d.). [accessed 2023 Jan 2]. Available from: https://www.who.int/.
  • Eve M, Gandawijaya J, Yang L, Oguro-Ando A. Neuronal cell adhesion molecules may mediate neuroinflammation in autism spectrum disorder. Front Psychiatry. 2022;13:842755. doi:10.3389/FPSYT.2022.842755.
  • Guerra DJ. The molecular genetics of autism spectrum disorders: genomic mechanisms, neuroimmunopathology, and clinical implications. Autism Res Treat. 2011;2011:398636), doi:10.1155/2011/398636.
  • Zawadska A, Magdalena C, Adamczyk A. The role of maternal immune activation in the pathogenesis of autism: a review of the evidence, proposed mechanisms and implications for treatment. Int J Mol Sci. 2021;22(21):11516. doi:10.3390/ijms222111516.
  • Lamy M, Erickson CA. Pharmacological management of behavioral disturbances in children and adolescents with autism spectrum disorders. Curr Probl Pediatr Adolesc Health Care. 2018;48(10):250–64. doi:10.1016/J.CPPEDS.2018.08.015.
  • Marcus RN, Owen R, Manos G, Mankoski R, Kamen L, McQuade RD, et al. Safety and tolerability of aripiprazole for irritability in pediatric patients with autistic disorder: a 52-week, open-label, multicenter study. J Clin Psychiatry. 2011;72(9):1270–6. doi:10.4088/JCP.09M05933.
  • Shea S, Turgay A, Carroll A, Schulz M, Orlik H, Smith I, et al. Risperidone in the treatment of disruptive behavioral symptoms in children with autistic and other pervasive developmental disorders. Pediatrics. 2004;114(5):634–41. doi:10.1542/PEDS.2003-0264-F.
  • Naber D, Lambert M. The CATIE and CUtLASS studies in schizophrenia: results and implications for clinicians. CNS Drugs. 2009;23(8):649–59. doi:10.2165/00023210-200923080-00002/METRICS.
  • Ghodke-Puranik Y, Thorn CF, Lamba JK, Leeder JS, Song W, Birnbaum AK, et al. Valproic acid pathway: pharmacokinetics and pharmacodynamics. Pharmacogenet Genomics. 2013;23(4):236–41. doi:10.1097/FPC.0B013E32835EA0B2.
  • Patterson PH. Modeling autistic features in animals. Pediatr Res. 2011;69(8):34–40. doi:10.1203/pdr.0b013e318212b80f.
  • Bambini-Junior V, Zanatta G, della Flora Nunes G, Mueller de Melo G, Michels M, Fontes-Dutra M, et al. Resveratrol prevents social deficits in animal model of autism induced by valproic acid. Neurosci Lett. 2014;583:176–81. doi:10.1016/J.NEULET.2014.09.039.
  • Cohen OS, Varlinskaya EI, Wilson CA, Glatt SJ, Mooney SM. Acute prenatal exposure to a moderate dose of valproic acid increases social behavior and alters gene expression in rats. Int J Dev Neurosci. 2013;31(8):740–50. doi:10.1016/J.IJDEVNEU.2013.09.002.
  • Martin HGS, Manzoni OJ. Late onset deficits in synaptic plasticity in the valproic acid rat model of autism. Front Cell Neurosci. 2014;8:23. doi:10.3389/fncel.2014.00023.
  • Kataoka S, Takuma K, Hara Y, Maeda Y, Ago Y, Matsuda T. Autism-like behaviours with transient histone hyperacetylation in mice treated prenatally with valproic acid. Int J Neuropsuchopharmacolog. 2013;16(1):91–103. doi:10.1017/S1461145711001714.
  • Gzielo K, Potasiewicz A, Hołuj M, Litwa E, Popik P, Nikiforuk A. Valproic acid exposure impairs ultrasonic communication in infant, adolescent and adult rats. Eur Neuropsychopharmacol. 2020;41:52–62. doi:10.1016/j.euroneuro.2020.09.006.
  • Schneider T, Roman A, Basta-Kaim A, Kubera M, Budziszewska B, Schneider K, Przewłocki R. Gender-specific behavioral and immunological alterations in an animal model of autism induced by prenatal exposure to valproic acid. Psychoneuroendocrinology. 2008;33(6):728–40. doi:10.1016/j.psyneuen.2008.02.011.
  • Dufour-Rainfray D, Vourc’h P, le Guisquet AM, Garreau L, Ternant D, Bodard S, et al. Behavior and serotonergic disorders in rats exposed prenatally to valproate: a model for autism. Neurosci Lett. 2010;470(1):55–9. doi:10.1016/J.NEULET.2009.12.054.
  • Narita N, Kato M, Tazoe M, Miyazaki K, Narita M, Okado N. Increased monoamine concentration in the brain and blood of fetal thalidomide- and valproic acid–exposed rat: putative animal models for autism. Pediatr Res. 2002;52(4):576–9. doi:10.1203/00006450-200210000-00018.
  • Kolozsi E, Mackenzie RN, Roullet FI, deCatanzaro D, Foster JA. Prenatal exposure to valproic acid leads to reduced expression of synaptic adhesion molecule neuroligin 3 in mice. Neuroscience. 2009;163(4):1201–10. doi:10.1016/j.neuroscience.2009.07.021.
  • Bringas ME, Carvajal-Flores FN, Lopez-Ramirez TA, Atzori M, Flores G. Rearrangement of the dendritic morphology in limbic regions and altered exploratory behavior in a rat model of autism spectrum disorder. Neuroscience. 2013;241:170–87. doi:10.1016/j.neuroscience.2013.03.030.
  • Rinaldi T, Silberberg G, Markram H. Hyperconnectivity of local neocortical microcircuitry induced by prenatal exposure to valproic acid. Cereb Cortex. 2008;18(4):763–70. doi:10.1093/cercor/bhm117.
  • Rinaldi T, Perrodin C, Markram H. Hyper-connectivity and hyper-plasticity in the medial prefrontal cortex in the valproic acid animal model of autism. Front Neural Circuits. 2008;2:4. doi:10.3389/neuro.04.004.2008.
  • Li X, Chauhan A, Sheikh AM, Patil S, Chauhan V, Li XM, et al. Elevated immune response in the brain of autistic patients. J Neuroimmunol. 2009;207(1–2):111–6. doi:10.1016/J.JNEUROIM.2008.12.002.
  • Kim UJ, Hong N, Ahn JC. Photobiomodulation attenuated cognitive dysfunction and neuroinflammation in a prenatal valproic acid-induced autism spectrum disorder mouse model. Int J Mol Sci. 2022;23(24):16099. doi:10.3390/ijms232416099.
  • Codagnone MG, Podesta MF, Uccelli NA, Reines A. Differential local connectivity and neuroinflammation profiles in the medial prefrontal cortex and hippocampus in the valproic acid rat model of autism. Dev Neurosci. 2015;37(3):215–31. doi:10.1159/000375489.
  • Baron-Cohen S, Ring H, Moriarty J, Schmitz B, Costa D, Ell P. Recognition of mental state terms. Clinical findings in children with autism and a functional neuroimaging study of normal adults. Br J Psychiatry. 1994;165(5):640–9. doi:10.1192/bjp.165.5.640.
  • Baron-Cohen S, Ring H, Wheelwright S, Bullmore ET, Brammer MJ, Simmons A, Williams SC. Social intelligence in the normal and autistic brain: an fMRI study. Eur J Neurosci. 1999;11(6):1891–8. doi:10.1046/j.1460-9568.1999.00621.x.
  • Banker S, Gu X, Schiller D, Foss-Feig J. Hippocampal contributions to social and cognitive deficits in autism spectrum disorder. Trends Neurosci. 2021;44(10):793–807. doi:10.1016/j.tins.2021.08.005.
  • Bourre JM, Dumont O, Piciotti M, Clément M, Chaudière J, Bonneil M, et al. Essentiality of omega 3 fatty acids for brain structure and function. World Rev Nutr Diet. 1991;66:103–17. doi:10.1159/000419283.
  • Haas HS, Schauenstein K. Immunity, hormones, and the brain. Allergy. 2001;56(6):470–7. doi:10.1034/J.1398-9995.2001.056006470.X.
  • Innis SM. Omega-3 fatty acid biochemistry: perspectives from human nutrition. Mil Med. 2014;179(suppl_11):82–7. doi:10.7205/MILMED-D-14-00147.
  • Bang HO, Dyerberg J, Nielsen AB. Plasma lipid and lipoprotein pattern in Greenlandic West-Coast Eskimos. Nutr Rev. 1986;44(4):143–6. doi:10.1111/J.1753-4887.1986.TB07607.X.
  • Dyerberg J, Bang HO, Stoffersen E, Moncada S, Vane JR. Eicosapentaenoic acid and prevention of thrombosis and atherosclerosis? Lancet. 1978;312(8081):117–9. doi:10.1016/S0140-6736(78)91505-2.
  • Raj P, Singh M, Rawat JK, Gautam S, Saraf SA, Kaithwas G. Effect of enteral administration of α-linolenic acid and linoleic acid against methotrexate induced intestinal toxicity in albino rats. RSC Adv. 2014;4(104):60397–403. doi:10.1039/C4RA10213D.
  • Kohli P, Levy BD. Resolvins and protectins: mediating solutions to inflammation. Br J Pharmacol. 2009;158(4):960–71. doi:10.1111/J.1476-5381.2009.00290.X.
  • Spite M, Clària J, Serhan CN. Resolvins, specialized proresolving lipid mediators, and their potential roles in metabolic diseases. Cell Metab. 2014;19(1):21–36. doi:10.1016/J.CMET.2013.10.006.
  • Kern JK, Jones AM. Evidence of toxicity, oxidative stress, and neuronal insult in autism. Journal of Toxicology and Environmental Health, Part B. 2007;9(6):485–99. doi:10.1080/10937400600882079.
  • Sajdel-Sulkowska EM, Xu M, Koibuchi N. Increase in cerebellar neurotrophin-3 and oxidative stress markers in autism. Cerebellum. 2009;8(3):366–72. doi:10.1007/S12311-009-0105-9/FIGURES/3.
  • Bahbah EI, Ghozy S, Attia MS, Negida A, Emran Tb, Mitra S, et al. Molecular mechanisms of astaxanthin as a potential neurotherapeutic agent. Mar Drugs. 2021;19(4):201. doi:10.3390/MD19040201.
  • Al-Amin MM, Rahman MM, Khan FR, Zaman F, Mahmud Reza H. Astaxanthin improves behavioral disorder and oxidative stress in prenatal valproic acid-induced mice model of autism. Behav Brain Res. 2015;286:112–21. doi:10.1016/J.BBR.2015.02.041.
  • Singh R, Kisku A, Kungumaraj H, Nagaraj V, Pal A, Kumar S, Sulakhiya K. Autism spectrum disorders: a recent update on targeting inflammatory pathways with natural anti-inflammatory agents. Biomedicines. 2023;11(1):115. doi:10.3390/biomedicines11010115.
  • Pangrazzi L, Balasco L, Bozzi Y. Natural antioxidants: a novel therapeutic approach to autism spectrum disorders? Antioxidants. 2020;9((12):1186. doi:10.3390/antiox9121186.
  • Veselinović A, Petrović S, Žikić V, Subotić M, Jakovljević V, Jeremić N, Vučić V. Neuroinflammation in autism and supplementation based on omega-3 polyunsaturated fatty acids: a narrative review. Medicina (B Aires). 2021;57(9):893. doi:10.3390/MEDICINA57090893.
  • Alfawaz H, Al-Onazi M, Bukhari SI, Binobead M, Othman N, Algahtani N, et al. The independent and combined effects of omega-3 and vitamin B12 in ameliorating propionic acid induced biochemical features in juvenile rats as rodent model of autism. J Mol Neurosci. 2018;66(3):403–13. doi:10.1007/s12031-018-1186-z.
  • Iwata K. Characterization of an animal model of autism and social interaction. Methods Mol Biol. 2019;1916:149–55. doi:10.1007/978-1-4939-8994-2_14.
  • Yang M, Silverman JL, Crawley JN. Automated three-chambered social approach task for mice. Curr Protoc Neurosci. 2011;doi:10.1002/0471142301.ns0826s56.
  • Bevins RA, Besheer J. Object recognition in rats and mice: a one-trial non-matching-to-sample learning task to study ‘recognition memory’. Nat Protoc. 2006;1(3):1306–11. doi:10.1038/nprot.2006.205.
  • Swerdlow NR. Prepulse inhibition of startle in humans and laboratory models. Encyclopedia of Neuroscience. Academic Press; . 2009. p. 947–55. doi:10.1016/B978-008045046-9.01938-0.
  • Mansbach RS, Geyer MA, Braff DL. Dopaminergic stimulation disrupts sensorimotor gating in the rat. Psychopharmacology (Berl). 1988;94(4):507–14. doi:10.1007/BF00212846.
  • Courchesne E, Mouton PR, Calhoun ME, Semendeferi K, Ahrens-Barbeau C, Hallet MJ, et al. Neuron number and size in prefrontal cortex of children with autism. JAMA. 2011;306(18):2001–10. doi:10.1001/jama.2011.1638.
  • Stoner R, Chow ML, Boyle MP, Sunkin SM, Mouton PR, Roy S, et al. Patches of disorganization in the neocortex of children with autism. N Engl J Med. 2014;370(13):1209–19. doi:10.1056/NEJMoa1307491.
  • Hashemi E, Ariza J, Rogers H, Noctor SC, Martínez-Cerdeño V. The number of parvalbumin-expressing interneurons is decreased in the medial prefrontal cortex in autism. Cereb Cortex. 2017;27(3):1931–43. doi:10.1093/cercor/bhw021.
  • Azmitia EC, Singh JS, Hou XP, Wegiel J. Dystrophic serotonin axons in postmortem brains from young autism patients. Anat Rec. 2011;294(10):1653–62. doi:10.1002/ar.21243.
  • Sheikh AM, Li X, Wen G, Tauqeer Z, Brown WT, Malik M. Cathepsin D and apoptosis related proteins are elevated in the brain of autistic subjects. Neuroscience. 2010;165(2):363–70. doi:10.1016/j.neuroscience.2009.10.035.
  • Takumi T, Tamada K, Hatanaka F, Nakai N, Bolton PF. Behavioral neuroscience of autism. Neurosci Biobehav Rev. 2020;110:60–76. doi:10.1016/J.NEUBIOREV.2019.04.012.
  • Du L, Zhao G, Duan Z, Li F. Behavioral improvements in a valproic acid rat model of autism following vitamin D supplementation. Psychiatry Res. 2017;253:28–32. doi:10.1016/J.PSYCHRES.2017.03.003.
  • Chaliha D, Albrecht M, Vaccarezza M, Takechi R, Lam V, Al-Salami H, Mamo J. A systematic review of the valproic-acid-induced rodent model of autism. Dev Neurosci. 2020;42(1):12–48. doi:10.1159/000509109.
  • Doaei S, Bourbour F, Teymoori Z, Jafari F, Kalantari N, Torki SA, et al. The effect of omega-3 fatty acids supplementation on social and behavioral disorders of children with autism: a randomized clinical trial. Pediatr Endocrinol Diabetes Metab. 2021;27(1):12–8. doi:10.5114/pedm.2020.101806.
  • Silverman JL, Oliver CF, Karras MN, Gastrell PT, Crawley JN. AMPAKINE enhancement of social interaction in the BTBR mouse model of autism. Neuropharmacology. 2013;64:268–82. doi:10.1016/J.NEUROPHARM.2012.07.013.
  • Bhattacharya A, Kaphzan H, Alvarez-Dieppa AC, Murphy JP, Pierre P, Klann E. Genetic removal of p70 S6 Kinase 1 corrects molecular, synaptic, and behavioral phenotypes in fragile X syndrome mice. Neuron. 2012;76(2):325–37. doi:10.1016/j.neuron.2012.07.022.
  • Taksima T, Chonpathompikunlert P, Sroyraya M, Hutamekalin P, Limpawattana M, Klaypradit W. Effects of astaxanthin from shrimp shell on oxidative stress and behavior in animal model of Alzheimer’s disease. Mar Drugs. 2019;17(11):628. doi:10.3390/MD17110628.
  • Rahman SO, Panda BP, Parvez S, Kaundal M, Hussain S, Akhtar M, Najmi AK. Neuroprotective role of astaxanthin in hippocampal insulin resistance induced by Aβ peptides in animal model of Alzheimer’s disease. Biomed Pharmacother. 2019;110:47–58. doi:10.1016/J.BIOPHA.2018.11.043.
  • de Andrade AM, Fernandes M da C, de Fraga LS, Porawski M, Giovenardi M, Guedes RP. Omega-3 fatty acids revert high-fat diet-induced neuroinflammation but not recognition memory impairment in rats. Metab Brain Dis. 2017;32(6):1871–81. doi:10.1007/S11011-017-0080-7/FIGURES/4.
  • Abd Allah E, Gomaa A, Sayed M. The effect of omega-3 on cognition in hypothyroid adult male rats. Acta Physiol Hung. 2014;101(3):362–76. doi:10.1556/APHYSIOL.101.2014.3.11.
  • Gao J, Wang X, Sun H, Cao Y, Liang S, Wang H, et al. Neuroprotective effects of docosahexaenoic acid on hippocampal cell death and learning and memory impairments in a valproic acid-induced rat autism model. Int J Dev Neurosci. 2016;49:67–78. doi:10.1016/j.ijdevneu.2015.11.006.
  • Schneider T, Przewłocki R. Behavioral alterations in rats prenatally exposed to valproic acid: animal model of autism. Neuropsychopharmacology. 2004;30(1):80–9. doi:10.1038/sj.npp.1300518.
  • Zugno AI, Chipindo HL, Volpato AM, Budni J, Steckert A, de Oliveira MB, et al. Omega-3 prevents behavior response and brain oxidative damage in the ketamine model of schizophrenia. Neuroscience. 2014;259:223–31. doi:10.1016/J.NEUROSCIENCE.2013.11.049.
  • Casquero-Veiga M, Romero-Miguel D, MacDowell KS, Torres-Sanchez S, Garcia-Partida JA, Lamanna-Rama N, et al. Omega-3 fatty acids during adolescence prevent schizophrenia-related behavioural deficits: neurophysiological evidences from the prenatal viral infection with Poly I:C. Eur Neuropsychopharmacol. 2021;46:14–27. doi:10.1016/J.EURONEURO.2021.02.001.
  • Davis JLB, O’connor M, Erlbacher H, Schlichte SL, Stevens HE. The impact of maternal antioxidants on prenatal stress effects on offspring neurobiology and behavior. Yale J Biol Med. 2022;95(1):87.
  • Matta SM, Hill-Yardin EL, Crack PJ. The influence of neuroinflammation in autism spectrum disorder. Brain Behav Immun. 2019;79:75–90. doi:10.1016/J.BBI.2019.04.037.
  • Cristiano C, Volpicelli F, Crispino M, Lacivita E, Russo R, Leopoldo M, et al. Behavioral, anti-inflammatory, and neuroprotective effects of a novel FPR2 agonist in two mouse models of autism. Pharmaceuticals. 2022;15(2):161. doi:10.3390/PH15020161/S1.
  • Elnahas EM, Abuelezz SA, Mohamad MI, Nabil MM, Abdelraouf SM, Bahaa N, et al. Validation of prenatal versus postnatal valproic acid rat models of autism: a behavioral and neurobiological study. Prog Neuro-Psychopharmacol Biol Psychiatr. 2021;108:110185. doi:10.1016/J.PNPBP.2020.110185.
  • Pardo CA, Charles GE. The neurobiology of autism. Brain Pathol. 2007;17(4):434–47. doi:10.1111/j.1750-3639.2007.00102.x.
  • Mazahery H, Stonehouse W, Delshad M, Kruger MC, Conlon CA, Beck KL, et al. Relationship between long chain n-3 polyunsaturated fatty acids and autism spectrum disorder: systematic review and meta-analysis of case-control and randomised controlled trials. Nutrients. 2017;9(2):155. doi:10.3390/nu9020155.
  • Amminger GP, Berger GE, Schäfer MR, Klier C, Friedrich MH, Feucht M. Omega-3 fatty acids supplementation in children with autism: a double-blind randomized, placebo-controlled pilot study. Biol Psychiatry. 2007;61(4):551–3. doi:10.1016/j.biopsych.2006.05.007.
  • Bent S, Hendren RL, Zandi T, Law K, Choi JE, Widjaja F, et al. Internet-based, randomized, controlled trial of omega-3 fatty acids for hyperactivity in autism. J Acad Child Adolesc Psychiatry. 2014;53(6):658–66. doi:10.1016/j.jaac.2014.01.018.
  • Voigt RG, Mellon MW, Katusic SK, Weaver AL, Matern D, Mellon B, et al. Dietary docosahexaenoic acid supplementation in children with autism. J Pediatr Gastroenterol Nutr. 2014;58(6):715–22. doi:10.1097/MPG.0000000000000260.
  • Kim RE, Shin CY, Han SH, Kwon KJ. Astaxanthin suppresses PM2.5-induced neuroinflammation by regulating Akt phosphorylation in BV-2 microglial cells. Int J Mol Sci. 2020;21(19):7227. doi:10.3390/IJMS21197227.
  • Wang S, Qi X. The putative role of astaxanthin in neuroinflammation modulation: mechanisms and therapeutic potential. Front Pharmacol. 2022;13:2458. doi:10.3389/FPHAR.2022.916653/BIBTEX.
  • Chang MX, Xiong F, Pak S, Liang Ooi S. Astaxanthin and its effects in inflammatory responses and inflammation-associated diseases: recent advances and future directions. Molecules. 2020;25(22):5342. doi:10.3390/MOLECULES25225342.
  • Naguib YM. Antioxidant activities of astaxanthin and related carotenoids. J Agric Food Chem. 2000;48(4):1150–4. doi:10.1021/jf991106k.
  • Barros MP, Poppe SC, Bondan EF. Neuroprotective properties of the marine carotenoid astaxanthin and omega-3 fatty acids, and perspectives for the natural combination of both in Krill oil. Nutrients. 2014;6(3):1293–317. doi:10.3390/nu6031293.
  • Shen H, Kuo C, Chou J, Delvolve A, Jackson SN, Post J, et al. Astaxanthin reduces ischemic brain injury in adult rats. FASEB J. 2009;23(6):1958–68. doi:10.1096/fj.08-123281.
  • Wu W, Wang X, Xiang Q, Meng X, Peng Y, Du N, et al. Astaxanthin alleviates brain aging in rats by attenuating oxidative stress and increasing BDNF levels. Food Funct 2014;5(1):158–66. doi:10.1039/c3fo60400d.
  • Madore C, Leyrolle Q, Lacabanne C, Benmamar-Badel A, Joffre C, Nadjar A, Laye S. Neuroinflammation in autism: plausible role of maternal inflammation, dietary omega 3, and microbiota. Neural Plast. 2016: 3597209. doi:10.1155/2016/3597209.
  • Kaliannan K, Wang B, Li X, Kim K, Kang JX. A host-microbiome interaction mediates the opposing effects of omega-6 and omega-3 fatty acids on metabolic endotoxemia. Sci Rep. 2015;5:11276. doi:10.1038/srep11276.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.