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Transport of Human Lactoferrin into Mouse Brain: Administration Routes and Distribution

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Bulletin of Experimental Biology and Medicine Aims and scope

We studied different ways of transport of human lactoferrin to the brain of C57Bl/6 mice after its administration via different routes, analyzed its distribution in the brain, and determined the phenotype of lactoferrin-containing cells. Colocalization of lactoferrin and markers of various cell types was estimated by fluorescent immunohistochemical analysis. Lactoferrin was detected in mouse brain sections after its intranasal, sublingual, and intraperitoneal administration, but not after conjunctival administration. After intranasal administration, lactoferrin rapidly penetrated into the brain and accumulated in the cytoplasm of vascular endothelial cells in the neocortex, striatum, hippocampus, and thalamus. After application of protein solution onto fixed floating sections, highly specific binding of lactoferrin was found in the nuclei of neurons, astrocytes, and microglia cells, but not in the nuclei of endothelial cells of mouse brain.

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References

  1. Bi C, Wang A, Chu Y, Liu S, Mu H, Liu W, Wu Z, Sun K, Li Y. Intranasal delivery of rotigotine to the brain with lactoferrinmodified PEG-PLGA nanoparticles for Parkinson’s disease treatment. Int. J. Nanomedicine. 2016;11:6547-6559.

    Article  CAS  Google Scholar 

  2. Conneely OM. Antiinflammatory activities of lactoferrin. J. Am. Coll. Nutr. 2001;20(5, Suppl):389S-395S.

    Article  CAS  Google Scholar 

  3. Elfinger M, Maucksch C, Rudolph C. Characterization of lactoferrin as a targeting ligand for nonviral gene delivery to airway epithelial cells. Biomaterials. 2007;28(23):3448-3455.

    Article  CAS  Google Scholar 

  4. Faraji N, Zhang Y, Ray AK. Determination of adsorption isotherm parameters for minor whey proteins by gradient elution preparative liquid chromatography. J. Chromatogr. A. 2015;1412:67-74.

    Article  CAS  Google Scholar 

  5. Fillebeen C, Descamps L, Dehouck MP, Fenart L, Benaïssa M, Spik G, Cecchelli R, Pierce A. Receptor-mediated transcytosis of lactoferrin through the blood-brain barrier. J. Biol. Chem. 1999;274(11):7011-7017.

    Article  CAS  Google Scholar 

  6. Fischer R, Debbabi H, Blais A, Dubarry M, Rautureau M, Boyaka PN, Tome D. Uptake of ingested bovine lactoferrin and its accumulation in adult mouse tissues. Int. Immunopharmacol. 2007;7(10):1387-1393.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  8. Hayashi T, To M, Saruta J, Sato C, Yamamoto Y, Kondo Y, Shimizu T, Kamata Y, Tsukinoki K. Salivary lactoferrin is transferred into the brain via the sublingual route. Biosci. Biotechnol. Biochem. 2017;81(7):1300-1304.

    Article  CAS  Google Scholar 

  9. Hu K, Li J, Shen Y, Lu W, Gao X, Zhang Q, Jiang X. Lactoferrin-conjugated PEG-PLA nanoparticles with improved brain delivery: in vitro and in vivo evaluations. J. Control. Release. 2009;134(1):55-61.

    Article  CAS  Google Scholar 

  10. Johnson EE, Wessling-Resnick M. Iron metabolism and the innate immune response to infection. Microbes Infect. 2012;14(3):207-216.

    Article  CAS  Google Scholar 

  11. Kamemori N, Takeuchi T, Sugiyama A, Miyabayashi M, Kitagawa H, Shimizu H, Ando K, Harada E. Trans-endothelial and trans-epithelial transfer of lactoferrin into the brain through BBB and BCSFB in adult rats. J. Vet. Med. Sci. 2008;70(3):313-315.

    Article  Google Scholar 

  12. Kumar V, Hassan M.I, Kashav T, Singh TP, Yadav S. Heparin-binding proteins of human seminal plasma: purification and characterization. Mol. Reprod. Dev. 2008;75(12):1767-1774.

    Article  CAS  Google Scholar 

  13. Kumari S, Ahsan SM, Kumar JM, Kondapi AK, Rao NM. Overcoming blood brain barrier with a dual purpose temozolomide loaded lactoferrin nanoparticles for combating glioma (SERP-17-12433). Sci. Rep. 2017;7(1). ID 6602. doi: https://doi.org/10.1038/s41598-017-06888-4

  14. Orsi N. The antimicrobial activity of lactoferrin: current status and perspectives. Biometals. 2004;17(3):189-196.

    Article  CAS  Google Scholar 

  15. Qian ZM, Wang Q. Expression of iron transport proteins and excessive iron accumulation in the brain in neurodegenerative disorders. Brain Res. Brain Res. Rev. 1998;27(3):257-267.

    Article  CAS  Google Scholar 

  16. Rosa L, Cutone A, Lepanto MS, Scotti MJ, Conte MP, Paesano R, Valenti P. Physico-chemical properties influence the functions and efficacy of commercial bovine lactoferrins. Biometals. 2018;31(3):301-312.

    Article  CAS  Google Scholar 

  17. Suzuki YA, Lopez V, Lönnerdal B. Mammalian lactoferrin receptors: structure and function. Cell. Mol. Life Sci. 2005;62(22):2560-2575.

    Article  CAS  Google Scholar 

  18. Thorne RG, Lakkaraju A, Rodriguez-Boulan E, Nicholson C. In vivo diffusion of lactoferrin in brain extracellular space is regulated by interactions with heparan sulfate. Proc. Natl Acad. Sci. USA. 2008;105(24):8416-8421.

    Article  Google Scholar 

  19. Tuccari G, Barresi G. Lactoferrin in human tumours: immunohistochemical investigations during more than 25 years. Biometals. 2011;24(5):775-784.

    Article  CAS  Google Scholar 

  20. Ward PP, Conneely OM. Lactoferrin: role in iron homeostasis and host defense against microbial infection. Biometals. 2004;17(3):203-208.

    Article  CAS  Google Scholar 

  21. Yan X, Xu L, Bi C, Duan D, Chu L, Yu X, Wu Z, Wang A, Sun K. Lactoferrin-modified rotigotine nanoparticles for enhanced nose-to-brain delivery: LESA-MS/MS-based drug biodistribution, pharmacodynamics, and neuroprotective effects. Int. J. Nanomedicine. 2018;13:273-281.

    Article  CAS  Google Scholar 

  22. Zhang Y, Lou F, Wu W, Dong X, Ren J, Shen Q. Determination of bovine lactoferrin in food by HPLC with a heparin affinity column for sample preparation. J. AOAC Int. 2017;100(1):133-138.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. National Research Center Kurchatov Institute, Moscow, Russia

    Yu. Kopaeva, A. B. Cherepov & I. Yu. Zarayskaya

  2. Lactobio Company, Moscow, Russia

    M. V. Nesterenko

Authors
  1. Yu. Kopaeva
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  2. A. B. Cherepov
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  3. I. Yu. Zarayskaya
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  4. M. V. Nesterenko
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Corresponding author

Correspondence to Yu. Kopaeva.

Additional information

Translated from Kletochnye Tekhnologii v Biologii i Meditsine, No. 2, pp. 106-113, June, 2019

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Kopaeva, Y., Cherepov, A.B., Zarayskaya, I.Y. et al. Transport of Human Lactoferrin into Mouse Brain: Administration Routes and Distribution. Bull Exp Biol Med 167, 561–567 (2019). https://doi.org/10.1007/s10517-019-04572-3

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  • DOI: https://doi.org/10.1007/s10517-019-04572-3

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