Advertisement

GeroScience

pp 1–11 | Cite as

Astaxanthin supplementation modulates cognitive function and synaptic plasticity in young and aged mice

  • Bethany Grimmig
  • Charles Hudson
  • Lauren Moss
  • Melinda Peters
  • Meena Subbarayan
  • Edwin J. Weeber
  • Paula C. BickfordEmail author
Original Article

Abstract

The incidence of neurodegenerative disorders and cognitive impairment is increasing. Rising prevalence of age-related medical conditions is associated with a dramatic economic burden; therefore, developing strategies to manage these health concerns is of great public health interest. Nutritionally based interventions have shown promise in treatment of these age-associated conditions. Astaxanthin is a carotenoid with reputed neuroprotective properties in the context of disease and injury, while emerging evidence suggests that astaxanthin may also have additional biological activities relating to neurogenesis and synaptic plasticity. Here, we investigate the potential for astaxanthin to modulate cognitive function and neural plasticity in young and aged mice. We show that feeding astaxanthin to aged mice for 1 month improves performance on several hippocampal-dependent cognitive tasks and increases long-term potentiation. However, we did not observe an alteration in neurogenesis, nor did we observe a change in microglial-associated IBA1 immunostaining. This demonstrates the potential for astaxanthin to modulate neural plasticity and cognitive function in aging.

Keywords

Aging Cognitive decline Inflammation Nutraceutical Neuroplasticity 

Abbreviations

AXT

Astaxanthin

BDNF

Brain-derived neurotrophic factor

LTP

Long-term potentiation

fEPSP

Field excitatory post synaptic potentials

PPF

Paired-pulse facilitation

DCX

Doublecortin

NPC

Neural progenitor cell

IBA1

Ionized calcium-binding adaptor protein

Notes

Funding

Funding was provided from the NIA R01 AG044919 (PCB) and the Veterans Administration I01 BX003421 (PCB).

Compliance with ethical standards

Disclaimer

The contents of this presentation do not represent the views of the Department of Veterans Affairs or the United States Government.

Conflict of interest

PCB is the co-Founder of Natura Therapeutics, Inc., and has served on the scientific advisory board for Nutrex Hawaii.

References

  1. Al-Amin MM et al (2016a) Astaxanthin ameliorates aluminum chloride-induced spatial memory impairment and neuronal oxidative stress in mice. Eur J Pharmacol 777:60–69.  https://doi.org/10.1016/j.ejphar.2016.02.062 Google Scholar
  2. Al-Amin MM, Sultana R, Sultana S, Rahman MM, Reza HM (2016b) Astaxanthin ameliorates prenatal LPS-exposed behavioral deficits and oxidative stress in adult offspring. BMC Neurosci 17:11.  https://doi.org/10.1186/s12868-016-0245-z Google Scholar
  3. Arvanitakis Z, Fleischman DA, Arfanakis K, Leurgans SE, Barnes LL, Bennett DA (2016) Association of white matter hyperintensities and gray matter volume with cognition in older individuals without cognitive impairment. Brain Struct Funct 221:2135–2146.  https://doi.org/10.1007/s00429-015-1034-7 Google Scholar
  4. Balietti M, Giannubilo SR, Giorgetti B, Solazzi M, Turi A, Casoli T, Ciavattini A, Fattorettia P (2016) The effect of astaxanthin on the aging rat brain: gender-related differences in modulating inflammation. J Sci Food Agric 96:615–618.  https://doi.org/10.1002/jsfa.7131 Google Scholar
  5. Bickford PC, Kaneko Y, Grimmig B, Pappas C, Small B, Sanberg CD, Sanberg PR, Tan J, Douglas Shytle R (2015) Nutraceutical intervention reverses the negative effects of blood from aged rats on stem cells. Age (Dordr) 37:103.  https://doi.org/10.1007/s11357-015-9840-7 Google Scholar
  6. Bickford PC, Flowers A, Grimmig B (2017) Aging leads to altered microglial function that reduces brain resiliency increasing vulnerability to neurodegenerative diseases. Exp Gerontol 94:4–8.  https://doi.org/10.1016/j.exger.2017.01.027 Google Scholar
  7. Binder DK, Scharfman HE (2004) Brain-derived neurotrophic factor. Growth Factors (Chur, Switzerland) 22:123–131.  https://doi.org/10.1080/08977190410001723308 Google Scholar
  8. Chang CH, Chen CY, Chiou JY, Peng RY, Peng CH (2010) Astaxanthine secured apoptotic death of PC12 cells induced by beta-amyloid peptide 25-35: its molecular action targets. J Med Food 13:548–556.  https://doi.org/10.1089/jmf.2009.1291 Google Scholar
  9. Choi HD, Kang HE, Yang SH, Lee MG, Shin WG (2011) Pharmacokinetics and first-pass metabolism of astaxanthin in rats. Br J Nutr 105:220–227.  https://doi.org/10.1017/S0007114510003454 Google Scholar
  10. Duvarci S, Pare D (2014) Amygdala microcircuits controlling learned fear. Neuron 82:966–980.  https://doi.org/10.1016/j.neuron.2014.04.042 Google Scholar
  11. Galasso C, Orefice I, Pellone P, Cirino P, Miele R, Ianora A, Brunet C, Sansone C (2018) On the neuroprotective role of astaxanthin: new perspectives? Marine drugs 16:247.  https://doi.org/10.3390/md16080247 Google Scholar
  12. Gite S, Ross RP, Kirke D, Guihéneuf F, Aussant J, Stengel DB, Dinan TG, Cryan JF, Stanton C (2018) Nutraceuticals to promote neuronal plasticity in response to corticosterone-induced stress in human neuroblastoma cells. Nutr Neurosci:1–18.  https://doi.org/10.1080/1028415X.2017.1418728
  13. Grimmig BA, Daly L, Hudson C, Nash K, Bickford PC (2017) Astaxanthin attenuates neurotoxicity in a mouse model of PD. Funct Foods Health Dis 7:562–567Google Scholar
  14. Grimmig B, Kim S-H, Nash K, Bickford PC, Douglas Shytle R (2017a) Neuroprotective mechanisms of astaxanthin: a potential therapeutic role in preserving cognitive function in age and neurodegeneration. GeroScience 39:19–32.  https://doi.org/10.1007/s11357-017-9958-x Google Scholar
  15. Grimmig B, Kim SH, Nash K, Bickford PC, Douglas Shytle R (2017b) Neuroprotective mechanisms of astaxanthin: a potential therapeutic role in preserving cognitive function in age and neurodegeneration. Geroscience 39:19–32.  https://doi.org/10.1007/s11357-017-9958-x Google Scholar
  16. Grimmig B, Daly L, Subbarayan M, Hudson C, Williamson R, Nash K, Bickford PC (2018) Astaxanthin is neuroprotective in an aged mouse model of Parkinson’s disease. Oncotarget 9:10388–10401.  https://doi.org/10.18632/oncotarget.23737 Google Scholar
  17. Guerin M, Huntley ME, Olaizola M (2003) Haematococcus astaxanthin: applications for human health and nutrition. Trends Biotechnol 21:210–216.  https://doi.org/10.1016/s0167-7799(03)00078-7 Google Scholar
  18. Ji X, Peng D, Zhang Y, Zhang J, Wang Y, Gao Y, Lu N, Tang P (2017) Astaxanthin improves cognitive performance in mice following mild traumatic brain injury. Brain Res 1659:88–95.  https://doi.org/10.1016/j.brainres.2016.12.031 Google Scholar
  19. Johnson EJ et al (2013) Relationship between serum and brain carotenoids, alpha-tocopherol, and retinol concentrations and cognitive performance in the oldest old from the Georgia Centenarian Study. J Aging Res 2013:951786.  https://doi.org/10.1155/2013/951786 Google Scholar
  20. Kidd P (2011) Astaxanthin, cell membrane nutrient with diverse clinical benefits and anti-aging potential. Altern Med Rev 16:355–364Google Scholar
  21. Kim YH, Koh HK, Kim DS (2010) Down-regulation of IL-6 production by astaxanthin via ERK-, MSK-, and NF-kappaB-mediated signals in activated microglia. Int Immunopharmacol 10:1560–1572.  https://doi.org/10.1016/j.intimp.2010.09.007 Google Scholar
  22. Kim B, Farruggia C, Ku CS, Pham TX, Yang Y, Bae M, Wegner CJ, Farrell NJ, Harness E, Park YK, Koo SI, Lee JY (2016) Astaxanthin inhibits inflammation and fibrosis in the liver and adipose tissue of mouse models of diet-induced obesity and nonalcoholic steatohepatitis. J Nutr Biochem 43:27–35.  https://doi.org/10.1016/j.jnutbio.2016.01.006 Google Scholar
  23. Lobos P, Bruna B, Cordova A, Barattini P, Galáz JL, Adasme T, Hidalgo C, Muñoz P, Paula-Lima A (2016) Astaxanthin protects primary hippocampal neurons against noxious effects of Aβ-oligomers. Neural Plasticity 2016:13.  https://doi.org/10.1155/2016/3456783 Google Scholar
  24. Lu Y, Xie T, He XX, Mao ZF, Jia LJ, Wang WP, Zhen JL, Liu LM (2015) Astaxanthin rescues neuron loss and attenuates oxidative stress induced by amygdala kindling in adult rat hippocampus. Neurosci Lett 597:49–53  https://doi.org/10.1016/j.neulet.2015.04.018 Google Scholar
  25. Manabe Y, Komatsu T, Seki S, Sugawara T (2018) Dietary astaxanthin can accumulate in the brain of rats. Biosci Biotechnol Biochem 82:1433–1436.  https://doi.org/10.1080/09168451.2018.1459467 Google Scholar
  26. Miller MG, Thangthaeng N, Poulose SM, Shukitt-Hale B (2017) Role of fruits, nuts, and vegetables in maintaining cognitive health. Exp Gerontol 94:24–28.  https://doi.org/10.1016/j.exger.2016.12.014 Google Scholar
  27. Nash KR, Moran P, Finneran DJ, Hudson C, Robinson J, Morgan D, Bickford PC (2015) Fractalkine over expression suppresses alpha-synuclein-mediated neurodegeneration. Mol Ther 23:17–23.  https://doi.org/10.1038/mt.2014.175 Google Scholar
  28. Norden DM, Godbout JP (2013) Microglia of the aged brain: primed to be activated and resistant to regulation. Neuropathol Appl Neurobiol 39:19–34.  https://doi.org/10.1111/j.1365-2990.2012.01306.x Google Scholar
  29. Paolicelli RC, Gross CT (2011) Microglia in development: linking brain wiring to brain environment. Neuron Glia Biol 7:77–83.  https://doi.org/10.1017/s1740925x12000105 Google Scholar
  30. Park JS, Mathison BD, Hayek MG, Zhang J, Reinhart GA, Chew BP (2013) Astaxanthin modulates age-associated mitochondrial dysfunction in healthy dogs. J Anim Sci 91:268–275.  https://doi.org/10.2527/jas.2012-5341 Google Scholar
  31. Qiao J, Rong L, Wang Z, Zhang M (2017) Involvement of Akt/GSK3beta/CREB signaling pathway on chronic omethoate induced depressive-like behavior and improvement effects of combined lithium chloride and astaxanthin treatment. Neurosci Lett 649:55–61.  https://doi.org/10.1016/j.neulet.2017.03.048 Google Scholar
  32. Schafer DP, Lehrman EK, Kautzman AG, Koyama R, Mardinly AR, Yamasaki R, Ransohoff RM, Greenberg ME, Barres BA, Stevens B (2012) Microglia sculpt postnatal neural circuits in an activity and complement-dependent manner. Neuron 74:691–705.  https://doi.org/10.1016/j.neuron.2012.03.026 Google Scholar
  33. Velkoff GVaV (2010) The next four decades The older population in the United States: 2010 to 2050 Current population reportsGoogle Scholar
  34. Wang HQ, Sun XB, Xu YX, Zhao H, Zhu QY, Zhu CQ (2010) Astaxanthin upregulates heme oxygenase-1 expression through ERK1/2 pathway and its protective effect against beta-amyloid-induced cytotoxicity in SH-SY5Y cells. Brain Res 1360:159–167.  https://doi.org/10.1016/j.brainres.2010.08.100 Google Scholar
  35. Wibrand K, Berge K, Messaoudi M, Duffaud A, Panja D, Bramham CR, Burri L (2013) Enhanced cognitive function and antidepressant-like effects after krill oil supplementation in rats. Lipids Health Dis 12:6.  https://doi.org/10.1186/1476-511x-12-6 Google Scholar
  36. Wu W, Wang X, Xiang Q, Meng X, Peng Y, du N, Liu Z, Sun Q, Wang C, Liu X (2014) Astaxanthin alleviates brain aging in rats by attenuating oxidative stress and increasing BDNF levels. Food Funct 5:158–166.  https://doi.org/10.1039/c3fo60400d Google Scholar
  37. Xu L, Zhu J, Yin W, Ding X (2015) Astaxanthin improves cognitive deficits from oxidative stress, nitric oxide synthase and inflammation through upregulation of PI3K/Akt in diabetes rat. Int J Clin Exp Pathol 8:6083–6094Google Scholar
  38. Yamashita E (2013) Astaxanthin as a medical food. Funct Foods Health Dis 3:254–258Google Scholar
  39. Yook JS, Okamoto M, Rakwal R, Shibato J, Lee MC, Matsui T, Chang H, Cho JY, Soya H (2016) Astaxanthin supplementation enhances adult hippocampal neurogenesis and spatial memory in mice. Mol Nutr Food Res 60:589–599.  https://doi.org/10.1002/mnfr.201500634 Google Scholar
  40. Zhang XS, Zhang X, Zhou ML, Zhou XM, Li N, Li W, Cong ZX, Sun Q, Zhuang Z, Wang CX, Shi JX (2014) Amelioration of oxidative stress and protection against early brain injury by astaxanthin after experimental subarachnoid hemorrhage. J Neurosurg 121:42–54.  https://doi.org/10.3171/2014.2.jns13730 Google Scholar
  41. Zhou X, Zhang F, Hu X, Chen J, Wen X, Sun Y, Liu Y, Tang R, Zheng K, Song Y (2015) Inhibition of inflammation by astaxanthin alleviates cognition deficits in diabetic mice. Physiol Behav 151:412–420.  https://doi.org/10.1016/j.physbeh.2015.08.015 Google Scholar

Copyright information

© This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2019

Authors and Affiliations

  1. 1.Department of Molecular Pharmacology and PhysiologyMorsani College of Medicine, USF HealthTampaUSA
  2. 2.Department of Neurosurgery and Brain RepairMorsani College of Medicine, USF HealthTampaUSA
  3. 3.Research ServiceJames A Haley Veterans HospitalTampaUSA

Personalised recommendations