Effects of human lactoferrin under conditions of neurotoxic exposure: experimental research

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Abstract

BACKGROUND: Translational research using laboratory animals aimed at revealing the features of the pathogenesis of Parkinson’s disease serve as a tool for finding new therapeutic strategies.

AIM: Was to investigate the effects of human lactoferrin (a multifunctional globular glycoprotein) on behavior the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated mice as the model of dopaminergic neurons loss.

MATERIALS AND METHODS: Nigrostriatal dopaminergic injury was induced by single administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (40 mg/kg) to five-month-old C57Bl/6 mice. Behavioral functions were assessed in the open field and rotarod tests and by the stride length analysis.

RESULTS: Preliminary administration of lactoferrin resulted in a significant reduction in the severity of nervous system lesions induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. The positive effect of lactoferrin on the exploratory behavior of animals disturbed by neurotoxin, depending on the time of administration, was revealed. Exogenous protein with double preliminary administration had a protective effect on the change in body weight of mice after acute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine exposure. This suggests a reduction in systemic toxic effects against the background of lactoferrin therapy.

CONCLUSION: The results obtained indicate the possibility of the potential use of lactoferrin as a promising therapeutic agent in the treatment of neurodegenerative diseases.

About the authors

Marina Yu. Kopaeva

National Research Center “Kurchatov Institute”

Author for correspondence.
Email: m.kopaeva@mail.ru
ORCID iD: 0000-0002-6100-2830
SPIN-code: 1480-6220
Scopus Author ID: 57211437591
ResearcherId: AAE-3285-2020

Researcher

Russian Federation, Moscow

Anton B. Cherepov

National Research Center “Kurchatov Institute”

Email: ipmagus@mail.ru
ORCID iD: 0000-0002-3757-5292
SPIN-code: 1465-2380
Scopus Author ID: 6507318449
ResearcherId: D-8053-2014

M.D., Lead Engineer

Russian Federation, Moscow

Irina Yu. Zarayskaya

National Research Center “Kurchatov Institute”

Email: irzar2003@mail.ru
ORCID iD: 0000-0003-2371-0227
SPIN-code: 6858-2891
Scopus Author ID: 55389409800

Ph.D. (Biology)

Russian Federation, Moscow

References

  1. Litvinenko IV, Trufanov AG, Yurin AA. Parkinson’s disease and parkinsonism syndromes. Kazan; 2018. 54 p.
  2. Dauer W, Przedborski S. Parkinson’s disease: mechanisms and models. Neuron. 2003;39(6):889–909. doi: 10.1016/s0896-6273(03)00568-3
  3. Sedelis M, Schwarting RK, Huston JP. Behavioral phenotyping of the MPTP mouse model of Parkinson’s disease. Behav Brain Res. 2001;125(1–2):109–125. doi: 10.1016/s0166-4328(01)00309-6
  4. Cao Q, Qin L, Huang F, et al. Amentoflavone protects dopaminergic neurons in MPTP-induced Parkinson’s disease model mice through PI3K/Akt and ERK signaling pathways. Toxicol Appl Pharmacol. 2017;319:80–90. doi: 10.1016/j.taap.2017.01.019
  5. Jackson-Lewis V, Przedborski S. Protocol for the MPTP mouse model of Parkinson’s disease. Nat Protoc. 2007;2(1):141–151. doi: 10.1038/nprot.2006.342
  6. Gubellini P, Kachidian P. Animal models of Parkinson’s disease: An updated overview. Rev Neurol (Paris). 2015;171(11):750–761. doi: 10.1016/j.neurol.2015.07.011
  7. García-Montoya IA, Cendón TS, Arévalo-Gallegos S, Rascón-Cruz Q. Lactoferrin a multiple bioactive protein: an overview. Biochim Biophys Acta. 2012;1820(3):226–236. doi: 10.1016/j.bbagen.2011.06.018
  8. Chen Y., Zheng Z., Zhu X., et al. Lactoferrin Promotes Early Neurodevelopment and Cognition in Postnatal Piglets by Upregulating the BDNF Signaling Pathway and Polysialylation. Mol Neurobiol. 2015;52(1):256–269. doi: 10.1007/s12035-014-8856-9
  9. Kopaeva MY, Alchinova IB, Nesterenko MV, et al. Lactoferrin beneficially influences the recovery of physiological and behavioral indexes in mice exposed to acute gamma-irradiation. Patogenez [Pathogenesis]. 2020;18(1):29–33. (In Russ.) doi: 10.25557/2310-0435.2020.01.29-33
  10. Kopaeva MY, Alchinova IB, Cherepov AB, et al. New Properties of a Well-Known Antioxidant: Pleiotropic Effects of Human Lactoferrin in Mice Exposed to Gamma Irradiation in a Sublethal Dose. Antioxidants (Basel). 2022; 11(9):1833. doi: 10.3390/antiox11091833
  11. Kopaeva MY, Cherepov AB, Nesterenko MV, Zarayskaya IY. Pretreatment with Human Lactoferrin Had a Positive Effect on the Dynamics of Mouse Nigrostriatal System Recovery after Acute MPTP Exposure. Biology (Basel). 2021;10(1):24. doi: 10.3390/biology10010024
  12. Faucheux BA, Nillesse N, Damier P, et al. Expression of lactoferrin receptors is increased in the mesencephalon of patients with Parkinson disease. Proc Natl Acad Sci USA. 1995;92(21):9603–9607. doi: 10.1073/pnas.92.21.9603
  13. Fillebeen C, Descamps L, Dehouck MP, et al. Receptor-mediated transcytosis of lactoferrin through the blood-brain barrier. J Biol Chem. 1999;274(11):7011–7017. doi: 10.1074/jbc.274.11.7011
  14. Suzuki YA, Lopez V, Lönnerdal B. Mammalian lactoferrin receptors: structure and function. Cell Mol Life Sci. 2005;62(22):2560–2575. doi: 10.1007/s00018-005-5371-1
  15. Rosa AI, Duarte-Silva S, Silva-Fernandes A, et al. Tauroursodeoxycholic Acid Improves Motor Symptoms in a Mouse Model of Parkinson’s Disease. Mol Neurobiol. 2018;55(12):9139–9155. doi: 10.1007/s12035-018-1062-4
  16. Mandillo S, Tucci V, Hölter SM, et al. Reliability, robustness, and reproducibility in mouse behavioral phenotyping: a cross-laboratory study. Physiol Genomics. 2008;34(3):243–255. doi: 10.1152/physiolgenomics.90207.2008
  17. Carola V, D’Olimpio F, Brunamonti E, Mangia F, Renzi P. Evaluation of the elevated plus-maze and open-field tests for the assessment of anxiety-related behaviour in inbred mice. Behav Brain Res. 2002;134(1–2):49–57. doi: 10.1016/s0166-4328(01)00452-1
  18. Ferger B, Teismann P, Earl CD, Kuschinsky K, Oertel WH. The protective effects of PBN against MPTP toxicity are independent of hydroxyl radical trapping. Pharmacol Biochem Behav. 2000;65(3): 425–431. doi: 10.1016/s0091-3057(99)00229-4
  19. Xu SF, Zhang YH, Wang S, et al. Lactoferrin ameliorates dopaminergic neurodegeneration and motor deficits in MPTP-treated mice. Redox Biol. 2019;21:101090. doi: 10.1016/j.redox.2018.101090
  20. Liu H, Wu H, Zhu N, et al. Lactoferrin protects against iron dysregulation, oxidative stress, and apoptosis in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson’s disease in mice. J Neurochem. 2020;152(3):397–415. doi: 10.1111/jnc.14857
  21. Rousseau E, Michel PP, Hirsch EC. The iron-binding protein lactoferrin protects vulnerable dopamine neurons from degeneration by preserving mitochondrial calcium homeostasis. Mol Pharmacol. 2013;84(6):888–898. doi: 10.1124/mol.113.087965
  22. Kopaeva MY, Azieva AM, Cherepov AB, et al. Human lactoferrin enhances the expression of transcription factor c-Fos in neuronal cultures under stimulated conditions. Patogenez [Pathogenesis]. 2021;19(1):74–78. (In Russ.) doi: 10.25557/2310-0435.2021.01.74-78

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2. Figure. Results of testing of mice in the OP at different time points after MFTP administration. LF/PBS was administered twice, 24 and 3 h before MFTP (a); 1 h before MFTP (b); 24 h after MFTP (c). Each point represents one animal. Data are presented as medians, quartiles, minimum and maximum values; * p < 0.05, ** p < 0.01, differences from control group; +p < 0.05, differences from the corresponding group that received LF at each moment

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