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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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BrdU found in microglia only in the control fed mice following LPS.Low magnification confocal photomicrographs were used to determine if the BrdU was labeling non-neural cells. (A–C) In the control animals without LPS the majority of the BrdU cells were not found to be microglia. (D–E) In the control diet fed rats treated with LPS note that fewer BrdU cells were found and that many of the BrdU labeled cells were microglia. White arrow shown in high magnification in Fig. 3D–F Yellow arrow shown in high magnification in Fig. 3G–I. (G–I) In the spirulina fed rats the BrdU cells were not found to be microglia.
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pone-0010496-g002: BrdU found in microglia only in the control fed mice following LPS.Low magnification confocal photomicrographs were used to determine if the BrdU was labeling non-neural cells. (A–C) In the control animals without LPS the majority of the BrdU cells were not found to be microglia. (D–E) In the control diet fed rats treated with LPS note that fewer BrdU cells were found and that many of the BrdU labeled cells were microglia. White arrow shown in high magnification in Fig. 3D–F Yellow arrow shown in high magnification in Fig. 3G–I. (G–I) In the spirulina fed rats the BrdU cells were not found to be microglia.

Mentions: The incorporation of BrdU in the DNA can occur in any cell that is actively synthesizing DNA. While incorporation of BrdU can occur in cells that are repairing DNA, it has been demonstrated that the amount of BrdU added to DNA during the repair process is typically below the level necessary to be detected by standard immunohistochemistry procedures [17]. BrdU does not discriminate proliferating neurons or glia. As LPS could increase the proliferation of glia, particularly microglia, confocal microscopy was used to determine if the BrdU was labeling glia. Figure 2 and 3, show the photomicrographs of BrdU (red) and Iba-1 (green). Iba-1 is a calcium-binding protein that is restrictedly expressed in macrophages/microglia [18]. In the neurogenic region of the hippocampus, BrdU+ cells were not found to be double labeled with Iba-1 to any measurable extent in control fed rats without LPS or in spirulina fed rats with LPS. However, in the control fed rats that were injected with LPS some BrdU+ cells were found in the SGZ that were double-labeled with Iba-1 (Fig. 2D–E, Fig. 3G–I).


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)

BrdU found in microglia only in the control fed mice following LPS.Low magnification confocal photomicrographs were used to determine if the BrdU was labeling non-neural cells. (A–C) In the control animals without LPS the majority of the BrdU cells were not found to be microglia. (D–E) In the control diet fed rats treated with LPS note that fewer BrdU cells were found and that many of the BrdU labeled cells were microglia. White arrow shown in high magnification in Fig. 3D–F Yellow arrow shown in high magnification in Fig. 3G–I. (G–I) In the spirulina fed rats the BrdU cells were not found to be microglia.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2864748&req=5

pone-0010496-g002: BrdU found in microglia only in the control fed mice following LPS.Low magnification confocal photomicrographs were used to determine if the BrdU was labeling non-neural cells. (A–C) In the control animals without LPS the majority of the BrdU cells were not found to be microglia. (D–E) In the control diet fed rats treated with LPS note that fewer BrdU cells were found and that many of the BrdU labeled cells were microglia. White arrow shown in high magnification in Fig. 3D–F Yellow arrow shown in high magnification in Fig. 3G–I. (G–I) In the spirulina fed rats the BrdU cells were not found to be microglia.
Mentions: The incorporation of BrdU in the DNA can occur in any cell that is actively synthesizing DNA. While incorporation of BrdU can occur in cells that are repairing DNA, it has been demonstrated that the amount of BrdU added to DNA during the repair process is typically below the level necessary to be detected by standard immunohistochemistry procedures [17]. BrdU does not discriminate proliferating neurons or glia. As LPS could increase the proliferation of glia, particularly microglia, confocal microscopy was used to determine if the BrdU was labeling glia. Figure 2 and 3, show the photomicrographs of BrdU (red) and Iba-1 (green). Iba-1 is a calcium-binding protein that is restrictedly expressed in macrophages/microglia [18]. In the neurogenic region of the hippocampus, BrdU+ cells were not found to be double labeled with Iba-1 to any measurable extent in control fed rats without LPS or in spirulina fed rats with LPS. However, in the control fed rats that were injected with LPS some BrdU+ cells were found in the SGZ that were double-labeled with Iba-1 (Fig. 2D–E, Fig. 3G–I).

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