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Stimulation of adult neural stem cells with a novel glycolipid biosurfactant

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An Erratum to this article was published on 10 September 2013

Abstract

Glycolipids are amphipathic molecules which are highly expressed on cell membranes in skin and brain where they mediate several key cellular processes. Neural stem cells are defined as undifferentiated, proliferative, multipotential cells with extensive self-renewal and are responsive to brain injury. Di-rhamnolipid: α-l-rhamnopyranosyl-(1-2)α-l-rhamnopyranosyl-3-hydroxydecanoyl-3-hydroxydecanoic acid, also referred to as di-rhamnolipid BAC-3, is a glycolipid isolated from the bacteria Pseudomonas aeruginosa. In the previous studies, di-rhamnolipid enhanced dermal tissue healing and regeneration. The present study provides the first assessment of di-rhamnolipid, and glycolipid biosurfactants in general, on the nervous system. Treatment of neural stem cells isolated from the lateral ventricle of adult mice and cultured in defined media containing growth factors at 0.5 and 1 μg/ml of di-rhamnolipid increased the number of neurospheres (2.7- and 2.8-fold, respectively) compared to controls and this effect remained even after passaging in the absence of di-rhamnolipid. In addition, neural stem cells treated with di-rhamnolipid at 50 and 100 μg/ml in defined media supplemented with fetal calf serum and without growth factors exhibited increased cell viability, indicating an interaction between di-rhamnolipid and serum components in the regulation of neural stem cells and neuroprogenitors. Intracerebroventricular administration of di-rhamnolipid at 300 and 120 ng/day increased the number of neurospheres (1.3- and 1.63-fold, respectively) that could be derived from the anterior lateral ventricles of adult mice. These results indicate that di-rhamnolipid stimulates proliferation of neural stem cells and increases their endogenous pools which may have therapeutic potential in managing neurodegenerative or neuropsychiatric disorders and promoting nervous tissue regeneration following injury.

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References

  1. Weiss S, Dunne C, Hewson J, Wohl C, Wheatley M, Paterson AC, Reynolds BA (1996) Multipotent CNS stem cells are present in the adult mammalian spinal cord and ventricular neuroaxis. J Neurosci 16:7599–7609

    PubMed  CAS  Google Scholar 

  2. Ikami T, Ishida H, Kiso M (2000) Synthesis and biological activity of glycolipids, with a focus on gangliosides and sulfatide analogs. Methods Enzymol 311:547–568

    PubMed  CAS  Google Scholar 

  3. Miyakoshi LM, Todeschini AR, Mendez-Otero R, Hedin-Pereira C (2012) Role of the 9-O-acetyl GD3 in subventricular zone neuroblast migration. Mol Cell Neurosci 49:240–249

    Article  PubMed  CAS  Google Scholar 

  4. Yanagisawa M, Taga T, Nakamura K, Ariga T, Yu RK (2005) Characterization of glycoconjugate antigens in mouse embryonic neural precursor cells. J Neurochem 95:1311–1320

    Article  PubMed  CAS  Google Scholar 

  5. Fantini J, Barrantes FJ (2009) Sphingolipid/cholesterol regulation of neurotransmitter receptor conformation and function. Biochim Biophys Acta 1788:2345–2361

    Article  PubMed  CAS  Google Scholar 

  6. Yu RK, Yanagisawa M (2007) Glycosignaling in neural stem cells: involvement of glycoconjugates in signal transduction modulating the neural stem cell fate. J Neurochem 103:39–46

    Article  PubMed  CAS  Google Scholar 

  7. Wennekes T, van den Berg RJBHN, Boot RG, van der Marel GA, Overkleeft HS, Aerts JMFG (2009) Glycosphingolipids—nature, function, and pharmacological modulation. Angew Chem Int Ed 48:8848–8869

    Article  CAS  Google Scholar 

  8. Yu RK, Nakatani Y, Yanagisawa M (2009) The role of glycosphingolipid metabolism in the developing brain. J Lipid Res 50:440–445

    Article  Google Scholar 

  9. Ariga T, McDonald MP, Yu RK (2008) Role of ganglioside metabolism in the pathogenesis of Alzheimer’s disease-a review. J Lipid Res 49:1157–1175

    Article  PubMed  CAS  Google Scholar 

  10. Kornhuber J, Reichel M, Tripal P, Groemer TW, Henkel AW, Mühle C, Gulbins E (2009) The role of ceramide in major depressive disorder. Eur Arch Psychiatry Clin Neurosci 259:199–204

    Article  Google Scholar 

  11. Narayan S, Head SR, Gilmartin TJ, Dean B, Thomas EA (2009) Evidence for disruption of sphingolipid metabolism in schizophrenia. J Neurosci Res 87:278–288

    Article  PubMed  CAS  Google Scholar 

  12. Valdomero A, Hansen C, de Burgos NG, Cuadra GR, Orsingher OA (2010) GM1 ganglioside enhances the rewarding properties of cocaine in rats. Eur J Pharmacol 630:79–83

    Article  PubMed  CAS  Google Scholar 

  13. Jarvis FG, Johnson MJ (1949) A glyco-lipid produced by Pseudomonas aeruginosa. J Am Chem Soc 71:4124–4126

    Article  CAS  Google Scholar 

  14. Maier RM, Soberon-Chavez G (2000) Pseudomonas aeruginosa rhamnolipids: biosynthesis and potential applications. Appl Microbiol Biotechnol 54:625–633

    Article  PubMed  CAS  Google Scholar 

  15. Rodrigues L, Banat IM, Teixeira J, Oliveira R (2006) Biosurfactants: potential applications in medicine. J Antimicrob Chemother 57:609–618

    Article  PubMed  CAS  Google Scholar 

  16. Stipcevic T, Piljac T, Isseroff RR (2005) Di-rhamnolipid from Pseudomonas aeruginosa displays differential effects on human keratinocyte and fibroblast cultures. J Dermatol Sci 40:141–143

    Article  PubMed  CAS  Google Scholar 

  17. Piljac G, Piljac V (1995a) Pharmaceutical preparation based on rhamnolipid. US Patent No. 5,466,675

  18. Piljac G, Piljac V (1995b) Immunological activity of rhamnolipids. US Patent No. 5,466,675

  19. Stipcevic T, Piljac A, Piljac G (2006) Enhanced healing of full-thickness burn wounds using di-rhamnolipid. Burns 32:24–34

    Article  PubMed  Google Scholar 

  20. Stipcevic T, Piljac T, Piljac J, Dujmic T, Piljac G (2006b) Use of rhamnolipids in wound healing, treatment and prevention of gum disease and periodontal regeneration. US Patent No. 7,129,218

  21. Piljac A, Stipcević T, Piljac-Zegarac J, Piljac G (2008) Successful treatment of chronic decubitus ulcer with 0.1 % dirhamnolipid ointment. J Cutan Med Surg 12:142–146

    PubMed  CAS  Google Scholar 

  22. Hitoshi S, Kippin T, van der Kooy D (2011) Culturing adult neural stem cells: application to the study of neurodegenerative and neuropsychiatric pathology. In: Seki T, Sawamoto K, Parent JM, Alvarez-Buylla A (eds) Neurogenesis in the adult brain II. Springer, Tokyo (JP), pp 189–207

    Chapter  Google Scholar 

  23. Kippin TE, Kapur S, van der Kooy D (2005) Dopamine specifically inhibits forebrain neural stem cell proliferation, suggesting a novel effect of antipsychotic drugs. J Neurosci 25:5815–5823

    Article  PubMed  CAS  Google Scholar 

  24. Kippin TE, Martens DJ, van der Kooy D (2005) p21 loss compromises the relative quiescence of forebrain stem cell proliferation leading to exhaustion of their proliferation capacity. Genes Dev 19:756–767

    Article  PubMed  CAS  Google Scholar 

  25. Venerando B, Roberti S, Sonnino S, Fiorilli A, Tettamanti G (1982) Interactions of ganglioside GM1 with human and fetal calf sera formation of ganglioside-serum albumin complexes. Biochim Biophys Acta 692:18–26

    Article  PubMed  CAS  Google Scholar 

  26. Schengrund CL, Mummert CM (1998) Exogenous gangliosides. How do they cross the blood-brain and how do they inhibit cell proliferation. Ann N Y Acad Sci 845:278–284

    Article  PubMed  CAS  Google Scholar 

  27. Hakomori SI (2002) The glycosynapse. Proc Natl Acad Sci USA 99:225–232

    Article  CAS  Google Scholar 

  28. Yanagisawa M, Yu RK (2009) The expression of glycoconjugates in neural stem cells. J Lipid Res 50:440–445

    Google Scholar 

  29. Iwabuchi K, Nakayama H, Iwahara C, Takamori K (2010) Significance of glycosphingolipid fatty acid chain length on membrane microdomain-mediated signal transduction. FEBS Lett 584:1642–1652

    Article  PubMed  CAS  Google Scholar 

  30. Mutoh T, Yano S, Yamamoto H (2004) Signal transduction mechanisms for the survival and death of neurons and muscle cells: modulation by membrane lipid rafts and their abnormality in the disorders of the nervous system. Nihon Shinkei Seishin Yakurigaku Zasshi 24:199–203

    PubMed  CAS  Google Scholar 

  31. Cabrera-Poch N, Sánchez-Ruiloba L, Rodriguez-Martinez M, Iglesias T (2004) Lipid raft disruption triggers protein kinase C and Src-dependent protein kinase D activation and Kidins220 phosphorylation in neuronal cells. J Biol Chem 279:28592–28602

    Article  PubMed  CAS  Google Scholar 

  32. Evans SV, MacKenzie CR (1999) Characterization of protein-glycolipid recognition at the membrane bilayer. J Mol Recognit 12:155–168

    Article  PubMed  CAS  Google Scholar 

  33. Young SZ, Taylor MM, Bordey A (2011) Neurotransmitters couple brain activity to subventricular zone neurogenesis. Eur J Neurosci 33:1123–1132

    Article  PubMed  Google Scholar 

  34. Bieberich E (2012) It’s a lipid’s world: bioactive lipid metabolism and signalling in neural stem cell differentiation. Neurochem Res 37:1208–1229

    Article  PubMed  CAS  Google Scholar 

  35. Seren S, Rubini R, Lazzaro A, Zanoni R, Fiori MG, Leon A (1990) Protective effects of a monosialoganglioside derivative following transitory forebrain ischemia in rats. Stroke 21:1607–1612

    Article  PubMed  CAS  Google Scholar 

  36. Figliomeni B, Bacci B, Panozzo C, Fogarolo F, Triban C, Fiori MG (1992) Experimental diabetic neuropathy: effect of ganglioside treatment on axonal transport of cytoskeletal proteins. Diabetes 41:866–871

    Article  PubMed  CAS  Google Scholar 

  37. Masuda Y, Sugiyama T (2000) The effect of globopentaosylceramide on a depression model, mouse forced swimming. Tohoku J Exp Med 191:47–54

    Article  PubMed  CAS  Google Scholar 

  38. Schneider JS, Sendek S, Daskalakis C, Cambi F (2010) GM1 ganglioside in Parkinson’s disease: results of a five year open study. J Neurol Sci 292:45–51

    Article  PubMed  CAS  Google Scholar 

  39. Stessin AM, Gursel DB, Schwartz A, Parashar B, Kulidzhanov FG, Sabbas AM, Boockvar J, Nori D, Wernicke AG (2012) FTY720, sphingosine 1-phosphate receptor modulator, selectively radioprotects hippocampal neural stem cells. Neurosci Lett 516:253–258

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This work was supported by National Institute on Drug Abuse grant DA027115. Paradigm Biomedical Inc. NY, USA is the owner of patents on rhamnolipids.

Conflict of interest

The authors declare no conflict of interest.

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Authors and Affiliations

  1. Department of Psychological and Brain Sciences, University of California Santa Barbara, Santa Barbara, CA, 93106-9660, USA

    Tamara Stipcevic, Christopher P. Knight & Tod E. Kippin

  2. Neuroscience Research Institute, University of California, Santa Barbara, CA, 93106-9660, USA

    Tamara Stipcevic & Tod E. Kippin

  3. Institute for Collaborative Biotechnology, University of California, Santa Barbara, CA, 93106-9660, USA

    Tod E. Kippin

Authors
  1. Tamara Stipcevic
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  2. Christopher P. Knight
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  3. Tod E. Kippin
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Correspondence to Tamara Stipcevic.

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Stipcevic, T., Knight, C.P. & Kippin, T.E. Stimulation of adult neural stem cells with a novel glycolipid biosurfactant. Acta Neurol Belg 113, 501–506 (2013). https://doi.org/10.1007/s13760-013-0232-4

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  • DOI: https://doi.org/10.1007/s13760-013-0232-4

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