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Spirulina promotes stem cell genesis and protects against LPS induced declines in neural stem cell proliferation.

Bachstetter AD, Jernberg J, Schlunk A, Vila JL, Hudson C, Cole MJ, Shytle RD, Tan J, Sanberg PR, Sanberg CD, Borlongan C, Kaneko Y, Tajiri N, Gemma C, Bickford PC - PLoS ONE (2010)

Bottom Line: We also have found that nutraceuticals have the potential to reduce neuroinflammation, and decrease oxidative stress.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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Pharmacology and Physiology, College of Medicine, University of South Florida, Tampa, Florida, United States of America.

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.

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Spirulina protects against LPS induced decrease in cell proliferation.(A) Results of the Stereological counts of the number of BrdU+ cells demonstrated that spirulina was able completely block the LPS induced decline in inflammation. *** p = 0.0049 (NIH-31 vs. NIH-31+LPS). ††† P = 0.0090 (NIH-31+LPS vs. spirulina+LPS). (B) Shows the representative BrdU staining in the rats without LPS. (C) After LPS in the rats fed the control diet there are fewer BrdU+ cells. (D) In the spirulina fed rat LPS did not cause a decrease in proliferation. (All photomicrographs taken at 10× magnification).
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pone-0010496-g001: Spirulina protects against LPS induced decrease in cell proliferation.(A) Results of the Stereological counts of the number of BrdU+ cells demonstrated that spirulina was able completely block the LPS induced decline in inflammation. *** p = 0.0049 (NIH-31 vs. NIH-31+LPS). ††† P = 0.0090 (NIH-31+LPS vs. spirulina+LPS). (B) Shows the representative BrdU staining in the rats without LPS. (C) After LPS in the rats fed the control diet there are fewer BrdU+ cells. (D) In the spirulina fed rat LPS did not cause a decrease in proliferation. (All photomicrographs taken at 10× magnification).

Mentions: Before induction of the LPS inflammatory insult, young adult male Fisher 344 rats were fed either a standard NIH-31 diet or a spirulina-enriched diet (NIH-31 +0.1% spirulina). After 28 days on the diets the rats were injected with LPS (1 mg/kg) into the peritoneal cavity to induce an acute inflammatory insult. The following day, day 29, the rats were injected twice (8 hours interval) with BrdU (50 mg/kg) to label those cells that were proliferating while BrdU was available. The rats were then euthanized on the following day to determine if spirulina could protect against the anti-neurogenic effects of LPS (see Fig. 1A for timeline). Quantification of the BrdU labeled cells, in the SGZ of the hippocampus, was performed using the optical fractionator method of design based stereology [15]. A significant effect was found (F(2,19) = 5.913, p<0.05) in the number of BrdU+ cells in the SGZ in the rats euthanized two days after the inflammatory insult of LPS (Fig. 1A). As we predicted, LPS did significantly decrease the number of BrdU+ cells in the rats fed the control diet (t(10) = 3.589; p = 0.0049). The cytokine storm induced by LPS peaks 2 hours after intraperitoneal injection of LPS [16], we found that even one full day after the peak of the cytokine storm, proliferation of the NPC was reduced by nearly 40% in rats fed the control diet. A diet enriched with spirulina was able to completely prevent the LPS induced decrease in NPC proliferation. In rats fed a spirulina enriched diet prior to being injected with LPS, proliferation of NPC was not significantly different then the control fed rats that were not injected with LPS. Moreover, in comparison to the control fed rats that were injected with LPS, the spirulina fed rats that were also injected with LPS had significantly more BrdU labeled cells in the SGZ (t(12) = 3.113; p = 0.0090).


Spirulina promotes stem cell genesis and protects against LPS induced declines in neural stem cell proliferation.

Bachstetter AD, Jernberg J, Schlunk A, Vila JL, Hudson C, Cole MJ, Shytle RD, Tan J, Sanberg PR, Sanberg CD, Borlongan C, Kaneko Y, Tajiri N, Gemma C, Bickford PC - PLoS ONE (2010)

Spirulina protects against LPS induced decrease in cell proliferation.(A) Results of the Stereological counts of the number of BrdU+ cells demonstrated that spirulina was able completely block the LPS induced decline in inflammation. *** p = 0.0049 (NIH-31 vs. NIH-31+LPS). ††† P = 0.0090 (NIH-31+LPS vs. spirulina+LPS). (B) Shows the representative BrdU staining in the rats without LPS. (C) After LPS in the rats fed the control diet there are fewer BrdU+ cells. (D) In the spirulina fed rat LPS did not cause a decrease in proliferation. (All photomicrographs taken at 10× magnification).
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2864748&req=5

pone-0010496-g001: Spirulina protects against LPS induced decrease in cell proliferation.(A) Results of the Stereological counts of the number of BrdU+ cells demonstrated that spirulina was able completely block the LPS induced decline in inflammation. *** p = 0.0049 (NIH-31 vs. NIH-31+LPS). ††† P = 0.0090 (NIH-31+LPS vs. spirulina+LPS). (B) Shows the representative BrdU staining in the rats without LPS. (C) After LPS in the rats fed the control diet there are fewer BrdU+ cells. (D) In the spirulina fed rat LPS did not cause a decrease in proliferation. (All photomicrographs taken at 10× magnification).
Mentions: Before induction of the LPS inflammatory insult, young adult male Fisher 344 rats were fed either a standard NIH-31 diet or a spirulina-enriched diet (NIH-31 +0.1% spirulina). After 28 days on the diets the rats were injected with LPS (1 mg/kg) into the peritoneal cavity to induce an acute inflammatory insult. The following day, day 29, the rats were injected twice (8 hours interval) with BrdU (50 mg/kg) to label those cells that were proliferating while BrdU was available. The rats were then euthanized on the following day to determine if spirulina could protect against the anti-neurogenic effects of LPS (see Fig. 1A for timeline). Quantification of the BrdU labeled cells, in the SGZ of the hippocampus, was performed using the optical fractionator method of design based stereology [15]. A significant effect was found (F(2,19) = 5.913, p<0.05) in the number of BrdU+ cells in the SGZ in the rats euthanized two days after the inflammatory insult of LPS (Fig. 1A). As we predicted, LPS did significantly decrease the number of BrdU+ cells in the rats fed the control diet (t(10) = 3.589; p = 0.0049). The cytokine storm induced by LPS peaks 2 hours after intraperitoneal injection of LPS [16], we found that even one full day after the peak of the cytokine storm, proliferation of the NPC was reduced by nearly 40% in rats fed the control diet. A diet enriched with spirulina was able to completely prevent the LPS induced decrease in NPC proliferation. In rats fed a spirulina enriched diet prior to being injected with LPS, proliferation of NPC was not significantly different then the control fed rats that were not injected with LPS. Moreover, in comparison to the control fed rats that were injected with LPS, the spirulina fed rats that were also injected with LPS had significantly more BrdU labeled cells in the SGZ (t(12) = 3.113; p = 0.0090).

Bottom Line: We also have found that nutraceuticals have the potential to reduce neuroinflammation, and decrease oxidative stress.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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Pharmacology and Physiology, College of Medicine, University of South Florida, Tampa, Florida, United States of America.

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.

Show MeSH
Related in: MedlinePlus