title: Spirulina promotes stem cell genesis and protects against LPS induced declines in neural stem cell proliferation.
abstract: Adult stem cells are present in many tissues including, skin, muscle, adipose, bone marrow, and in the brain. Neuroinflammation has been shown to be a potent negative regulator of stem cell and progenitor cell proliferation in the neurogenic regions of the brain. Recently we demonstrated that decreasing a key neuroinflammatory cytokine IL-1beta in the hippocampus of aged rats reversed the age-related cognitive decline and increased neurogenesis in the age rats. We also have found that nutraceuticals have the potential to reduce neuroinflammation, and decrease oxidative stress. The objectives of this study were to determine if spirulina could protect the proliferative potential of hippocampal neural progenitor cells from an acute systemic inflammatory insult of lipopolysaccharide (LPS). To this end, young rats were fed for 30 days a control diet or a diet supplemented with 0.1% spirulina. On day 28 the rats were given a single i.p. injection of LPS (1 mg/kg). The following day the rats were injected with BrdU (50 mg/kg b.i.d. i.p.) and were sacrificed 24 hours after the first injection of BrdU. Quantification of the BrdU positive cells in the subgranular zone of the dentate gyrus demonstrated a decrease in proliferation of the stem/progenitor cells in the hippocampus as a result of the LPS insult. Furthermore, the diet supplemented with spirulina was able to negate the LPS induced decrease in stem/progenitor cell proliferation. In a second set of studies we examined the effects of spirulina either alone or in combination with a proprietary formulation (NT-020) of blueberry, green tea, vitamin D3 and carnosine on the function of bone marrow and CD34+ cells in vitro. Spirulina had small effects on its own and more than additive effects in combination with NT-020 to promote mitochondrial respiration and/or proliferation of these cells in culture. When examined on neural stem cells in culture spirulina increased proliferation at baseline and protected against the negative influence of TNFalpha to reduce neural stem cell proliferation. These results support the hypothesis that a diet enriched with spirulina and other nutraceuticals may help protect the stem/progenitor cells from insults.
authors.affiliation: Department of Molecular Pharmacology and Physiology, College of Medicine, University of South Florida, Tampa, Florida, United States of America.
authors.forename: Adam D
authors.initials: AD
authors.lastname: Bachstetter
authors.forename: Jennifer
authors.initials: J
authors.lastname: Jernberg
authors.forename: Andrea
authors.initials: A
authors.lastname: Schlunk
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Vila
authors.forename: Charles
authors.initials: C
authors.lastname: Hudson
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Cole
authors.forename: R Douglas
authors.initials: RD
authors.lastname: Shytle
authors.forename: Jun
authors.initials: J
authors.lastname: Tan
authors.forename: Paul R
authors.initials: PR
authors.lastname: Sanberg
authors.forename: Cyndy D
authors.initials: CD
authors.lastname: Sanberg
authors.forename: Cesario
authors.initials: C
authors.lastname: Borlongan
authors.forename: Yuji
authors.initials: Y
authors.lastname: Kaneko
authors.forename: Naoki
authors.initials: N
authors.lastname: Tajiri
authors.forename: Carmelina
authors.initials: C
authors.lastname: Gemma
authors.forename: Paula C
authors.initials: PC
authors.lastname: Bickford
mesh_terms: D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D051379:Mice; D017628:Microglia / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D053545:Spirulina / Q000187:drug effects / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D005904:Glial Fibrillary Acidic Protein; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D001973:Bromodeoxyuridine
references.citation: Am J Physiol Regul Integr Comp Physiol. 2000 Feb;278(2):R331-6
references.pmid: 10666132
references.citation: J Leukoc Biol. 2005 Dec;78(6):1233-41
references.pmid: 16314440
references.citation: Aging Cell. 2008 Aug;7(4):569-89
references.pmid: 18221417
references.citation: Proc Natl Acad Sci U S A. 2008 Jan 15;105(2):751-6
references.pmid: 18178625
references.citation: Immunopharmacol Immunotoxicol. 1996 Aug;18(3):457-63
references.pmid: 8872496
references.citation: J Neurosci. 2008 Nov 19;28(47):12477-88
references.pmid: 19020040
references.citation: Rejuvenation Res. 2007 Jun;10(2):173-8
references.pmid: 17518694
references.citation: Nat Neurosci. 2007 Sep;10(9):1110-5
references.pmid: 17726477
references.citation: Exp Neurol. 2005 May;193(1):75-84
references.pmid: 15817266
references.citation: Planta Med. 2001 Nov;67(8):737-42
references.pmid: 11731916
references.citation: Vopr Pitan. 2007;76(2):21-5
references.pmid: 17561650
references.citation: Proc Natl Acad Sci U S A. 2003 Nov 11;100(23):13632-7
references.pmid: 14581618
references.citation: Aust J Exp Biol Med Sci. 1975 Feb;53(1):59-63
references.pmid: 1147854
references.citation: J Neurosci. 2002 Jul 15;22(14):6114-20
references.pmid: 12122072
references.citation: Anat Rec. 1991 Dec;231(4):482-97
references.pmid: 1793176
references.citation: J Med Food. 2008 Jun;11(2):313-22
references.pmid: 18598175
references.citation: Int Immunopharmacol. 2006 Dec 5;6(12):1808-14
references.pmid: 17052671
references.citation: J Immunol. 1993 Apr 1;150(7):2659-67
references.pmid: 8454848
references.citation: Biochem Biophys Res Commun. 2000 Nov 2;277(3):599-603
references.pmid: 11062000
references.citation: Immunopharmacol Immunotoxicol. 1996 Aug;18(3):465-76
references.pmid: 8872497
references.citation: Rejuvenation Res. 2008 Feb;11(1):201-14
references.pmid: 18260778
references.citation: Stem Cells. 2008 Sep;26(9):2361-71
references.pmid: 18583543
references.citation: Exp Neurol. 2005 Dec;196(2):298-307
references.pmid: 16176814
references.citation: J Comp Neurol. 1997 Nov 10;388(1):106-19
references.pmid: 9364241
references.citation: Science. 2003 Dec 5;302(5651):1760-5
references.pmid: 14615545
references.citation: Brain Res Rev. 2007 Jan;53(1):198-214
references.pmid: 17020783
references.citation: Brain Res Mol Brain Res. 1998 Jun 1;57(1):1-9
references.pmid: 9630473
references.citation: Hippocampus. 2006;16(3):216-24
references.pmid: 16421862
references.citation: Stem Cells Dev. 2006 Feb;15(1):118-23
references.pmid: 16522169
references.citation: Science. 2009 Jul 10;325(5937):210-3
references.pmid: 19590004
references.citation: Glia. 2001 Nov;36(2):165-79
references.pmid: 11596125
references.citation: J Neurosci. 2006 Sep 20;26(38):9703-12
references.pmid: 16988041