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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 increases proliferation of human neural stem cells in vitro and protects against a TNFα insult.Human neural progenitors grown under proliferation conditions were assessed by MTT assay (A) or BrdU (B) for the effects of spirulina (125 ng/ml) or NT-020 (500 ng/ml) or the two treatments combined in the presence or absence of TNFα (20 ng/ml) for 72 hours. (A) The MTT assay shows that spirulina alone or NT-020 alone increase proliferation; surprising, the in combination proliferation is decrease compare to control ** p<0.005(compare to media alone). Addition of 20 ng/ml human recombinant TNFα significantly decreased proliferation compare to media alone (***p<0.0001). Only the addition of spirulina alone was able to revert decrease in proliferation †††p<0.05 (compare to TNFα alone). (B) Spirulina and NT-020 alone significantly increased the number of BrdU+ cells. When added together spirulina and NT-020 cause a significant decrease in proliferation ** p<0.005 ***p<0.0001 (compare to media alone). The addition of TNFα significantly decreased proliferation compare to media alone (***p<0.0001). Spirulina alone was able to prevent the decrease in the number of BrdU+ cells. ††† p<0.0001 (compare to TNFα alone).
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pone-0010496-g007: Spirulina increases proliferation of human neural stem cells in vitro and protects against a TNFα insult.Human neural progenitors grown under proliferation conditions were assessed by MTT assay (A) or BrdU (B) for the effects of spirulina (125 ng/ml) or NT-020 (500 ng/ml) or the two treatments combined in the presence or absence of TNFα (20 ng/ml) for 72 hours. (A) The MTT assay shows that spirulina alone or NT-020 alone increase proliferation; surprising, the in combination proliferation is decrease compare to control ** p<0.005(compare to media alone). Addition of 20 ng/ml human recombinant TNFα significantly decreased proliferation compare to media alone (***p<0.0001). Only the addition of spirulina alone was able to revert decrease in proliferation †††p<0.05 (compare to TNFα alone). (B) Spirulina and NT-020 alone significantly increased the number of BrdU+ cells. When added together spirulina and NT-020 cause a significant decrease in proliferation ** p<0.005 ***p<0.0001 (compare to media alone). The addition of TNFα significantly decreased proliferation compare to media alone (***p<0.0001). Spirulina alone was able to prevent the decrease in the number of BrdU+ cells. ††† p<0.0001 (compare to TNFα alone).

Mentions: We next examined the effects of the most effective dose of spirulina (125 ng/ml) and or NT-020 in the presence or absence of TNFα to determine if the effects observed in vivo to promote neurogenesis would be observed in vitro. In Figure 7A a significant effect was found by MTT assay (F(7,57) = 59.83, p<0.0001). It can be observed that spirulina and NT-020 both increase proliferation of human neural stem cells in culture at baseline when measured with the MTT assay. When TNFα was added to the media this reduced the proliferation by approximately 40%, however spirulina, but not NT was able to block this effect in vitro. In the human neural stem cells as opposed to the hematopoetic stem cells there was no additive effect of spirulina and NT-020. To determine if this effect was also observed with a more direct measure of proliferation duplicate cultures were quantified for proliferation using BrdU. As can be observed in Figure 7B a significant effect was found by BrdU (F(7,47) = 252.4, p<0.0001). These data reflect that spirulina and NT-020 increased the numbers of cells dividing in these cultures and that TNFα reduced the proliferation of cells and that spirulina but not NT-020 had an effect to reduce the inhibition by TNFα.


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 increases proliferation of human neural stem cells in vitro and protects against a TNFα insult.Human neural progenitors grown under proliferation conditions were assessed by MTT assay (A) or BrdU (B) for the effects of spirulina (125 ng/ml) or NT-020 (500 ng/ml) or the two treatments combined in the presence or absence of TNFα (20 ng/ml) for 72 hours. (A) The MTT assay shows that spirulina alone or NT-020 alone increase proliferation; surprising, the in combination proliferation is decrease compare to control ** p<0.005(compare to media alone). Addition of 20 ng/ml human recombinant TNFα significantly decreased proliferation compare to media alone (***p<0.0001). Only the addition of spirulina alone was able to revert decrease in proliferation †††p<0.05 (compare to TNFα alone). (B) Spirulina and NT-020 alone significantly increased the number of BrdU+ cells. When added together spirulina and NT-020 cause a significant decrease in proliferation ** p<0.005 ***p<0.0001 (compare to media alone). The addition of TNFα significantly decreased proliferation compare to media alone (***p<0.0001). Spirulina alone was able to prevent the decrease in the number of BrdU+ cells. ††† p<0.0001 (compare to TNFα alone).
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2864748&req=5

pone-0010496-g007: Spirulina increases proliferation of human neural stem cells in vitro and protects against a TNFα insult.Human neural progenitors grown under proliferation conditions were assessed by MTT assay (A) or BrdU (B) for the effects of spirulina (125 ng/ml) or NT-020 (500 ng/ml) or the two treatments combined in the presence or absence of TNFα (20 ng/ml) for 72 hours. (A) The MTT assay shows that spirulina alone or NT-020 alone increase proliferation; surprising, the in combination proliferation is decrease compare to control ** p<0.005(compare to media alone). Addition of 20 ng/ml human recombinant TNFα significantly decreased proliferation compare to media alone (***p<0.0001). Only the addition of spirulina alone was able to revert decrease in proliferation †††p<0.05 (compare to TNFα alone). (B) Spirulina and NT-020 alone significantly increased the number of BrdU+ cells. When added together spirulina and NT-020 cause a significant decrease in proliferation ** p<0.005 ***p<0.0001 (compare to media alone). The addition of TNFα significantly decreased proliferation compare to media alone (***p<0.0001). Spirulina alone was able to prevent the decrease in the number of BrdU+ cells. ††† p<0.0001 (compare to TNFα alone).
Mentions: We next examined the effects of the most effective dose of spirulina (125 ng/ml) and or NT-020 in the presence or absence of TNFα to determine if the effects observed in vivo to promote neurogenesis would be observed in vitro. In Figure 7A a significant effect was found by MTT assay (F(7,57) = 59.83, p<0.0001). It can be observed that spirulina and NT-020 both increase proliferation of human neural stem cells in culture at baseline when measured with the MTT assay. When TNFα was added to the media this reduced the proliferation by approximately 40%, however spirulina, but not NT was able to block this effect in vitro. In the human neural stem cells as opposed to the hematopoetic stem cells there was no additive effect of spirulina and NT-020. To determine if this effect was also observed with a more direct measure of proliferation duplicate cultures were quantified for proliferation using BrdU. As can be observed in Figure 7B a significant effect was found by BrdU (F(7,47) = 252.4, p<0.0001). These data reflect that spirulina and NT-020 increased the numbers of cells dividing in these cultures and that TNFα reduced the proliferation of cells and that spirulina but not NT-020 had an effect to reduce the inhibition by TNFα.

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