• Nutrition Research and Practice
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• v.11 no.1
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• pp.25-32
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• 2017

BACKGROUND/OBJECTIVES: Stress-induced cognitive impairment is related to the suppression of hippocampal neurogenesis that results from an increase of oxidative stress. Therefore, the aim of this study was to investigate the effects of administration of a blueberry drink, having a high antioxidant power, on the cognitive performance of adult rats exposed to chronic mild stress. MATERIALS/METHODS: Twelve-week-old male Sprague-Dawley rats (n = 48) were randomly divided into four groups: control (CO), stress (ST), control + 5% blueberry drink (CO + B), and stress + 5% blueberry drink (ST + B). After eight weeks, the cognitive performance was assessed using a multiple T-maze water test. Levels of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and ascorbic acid were measured in the brain, and catecholamine concentrations were measured in plasma. RESULTS: The brain weights of the rats from the ST and ST + B groups were significantly lower than those of the rats from the CO and CO + B groups. The cognitive performance of the ST group was impaired when compared to that of the CO group. This impairment was significantly improved by the blueberry drink supplementation (P < 0.05). The brain SOD and CAT concentrations were not influenced by the stress or by the blueberry drink. However, the brain levels of GPx and ascorbic acid were significantly lower in the ST group than those in the CO group and were increased by the blueberry drink supplementation. The plasma catecholamine concentrations were affected by chronic mild stress and by the blueberry drink. The plasma norepinephrine and dopamine concentrations were decreased by the chronic stress and improved by the blueberry drink supplementation. The plasma epinephrine level was only influenced by the stress. CONCLUSION: These findings suggest that the blueberry drink may protect against the cognitive impairment induced by chronic mild stress.

• Molecules and Cells
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• v.19 no.1
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• pp.74-80
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• 2005

Stress is known to inhibit granule cell proliferation in the hippocampus. However, recent studies suggest that the commonly used dose of bromodeoxyuridine (BrdU) is insufficient to label all fractions of granule cells. Furthermore, stress-induced changes in BrdU availability may influence the labeling of newly born cells. To investigate whether changes in BrdU availability affect measurements of stress-induced granule cell proliferation, granule cell proliferation was assessed using injection of high doses of BrdU before and after restraint stress lasting 1 h. In addition, to determine whether stress-induced changes in plasma corticosterone levels were influenced by the BrdU, time-dependent changes in plasma corticosterone levels over 2 h after BrdU injection were compared with total accumulated plasma corticosterone levels [as determined by areas under the curve (AUC)]. Restraint stress significantly reduced the numbers of BrdU-labeled cells and clusters in the granule cell layer (GCL) of rats that received BrdU after stress, and decreases of similar magnitude were observed when the rats were given BrdU before stress. BrdU injection enhanced the stress-induced plasma corticosterone response, but there was no difference between the mean AUCs of plasma corticosterone levels of animals injected with BrdU before or after stress. These observations suggest that restraint stress decreases granule cell proliferation, and that this may be influenced by the extent and duration of plasma corticosterone increases rather than by changes in the availability of BrdU.

• Proceedings of the Ginseng society Conference
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• 2002.10a
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• pp.522-530
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• 2002

We have already known, neural progenitor cells exist not only in the developing brain, but in certain spots in adult CNS in mammals, so it will be of great value to find out some compounds which can interfere these cells proliferation ability. In this research, we observed that ginsenoside $Rg_1$ can not only enhance neural progenitors' proliferation ability in vitro, but increase neurogenesis in adult mouse dentate gyrus in vivo. Firstly, we set up neural progenitor cells' culture system from embryonic rats' hippocampus and prove their feature through immunocytochemistry. Then by using MTT assay, we found that when growing with ginsenoside $Rg_1(0.5\~2.5{\mu}mol/l)$, the progenitor cells' survival rate nearly doubled, furthermore, we proved that this increase was due to the increment of cell proliferation through $^3H-thimidine$ incorporation assay, hence, we drew the first conclusion: ginsenoside Rg1 has the ability to stimulate neural progenitor cells' proliferation in vitro; in order to observe this compound's effect in vivo, we devised the following experiment: after administering ginsenoside Rg1 (5, 10 mg/kg, once a day) intraperitoneally for two weeks, we examine the number of BrdU positive cells in the dentate gyrus of mice, and found that Rg1 could increase the number of proliferation cells significantly in vivo. From these studies, we are quite sure about Rg1's effects on the proliferation ability of neural progenitor cells both in vitro and in vivo, certain targets of the compound and its underlying mechanisms are in progress.

• Journal of Life Science
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• v.26 no.1
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• pp.8-16
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• 2016

Reactive oxygen species (ROS), at appropriate concentrations, mediate various normal cellular functions, including defense against pathogens, signal transduction, cellular growth, and gene expression. A recent study demonstrated that ROS and ROS-generating NADPH oxidase (Nox) are important in self-renewal and neuronal differentiation of subventricular zone (SVZ) neural stem cells in adult mouse brains. In this study, we found that endogenous ROS were detected in SVZ neural stem cells cultured from postnatal mouse brains. Nox4 was predominantly expressed in cultured cells, while the levels of the Nox1 and Nox2 transcripts were very low. In addition, the Nox4 gene was highly upregulated (by up to 10-fold) during neuronal differentiation. Immunocytochemical analysis detected the Nox4 protein mainly in neurons positive for the neuronal specific tubulin Tuj1. After differentiation, endogenous ROS were detected exclusively in neuron-like cells with processes. In addition, perturbation of the cellular redox state with N-acetyl cysteine, a ROS scavenger, during neuronal differentiation greatly inhibited neurogenesis. Lastly, knockdown of Nox4 using short hairpin RNA decreased neurogenesis. These findings suggest that Nox4 may be a major ROS-generating enzyme in postnatal SVZ neural stem cells, and Nox4-mediated ROS generation may be important in their neuronal differentiation.

• BMB Reports
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• v.44 no.12
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• pp.793-798
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• 2011

Recently, pluripotency induction or cellular reprogramming by introducing critical transcription factors has been extensively studied, but has been demonstrated only in vitro. Based on reports that Oct4 is critically involved in transforming neural stem cells into pluripotent cells, we used the lentiviral vector to introduce the Oct4 gene into the hippocampal dentate gyrus (DG) of adult mice. We examined whether this manipulation led to cellular or behavioral changes, possibly through processes involving the transformation of NS cells into pluripotent cells. The Oct4 lentivirus-infused group and the green fluorescent protein lentivirus-infused group showed a similar thickness of the DG and a comparable level of synaptophysin expression in the DG. Furthermore, our behavioral analyses did not show any differences between the groups concerning exploratory activity, anxiety, or memory abilities. This first trial for pluripotency induction in vivo, despite negative results, provides implications and information for future studies on in vivo cellular reprogramming.

• Journal of Ginseng Research
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• v.46 no.3
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• pp.408-417
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• 2022

Background: Korean Red Ginseng extract (KRGE) has been used as a health supplement and herbal medicine. Astrocytes are one of the key cells in the central nervous system (CNS) and have bioenergetic potential as they stimulate mitochondrial biogenesis. They play a critical role in connecting the brain vasculature and nerves in the CNS. Methods: Brain samples from KRGE-administered mice were tested using immunohistochemistry. Treatment of human brain astrocytes with KRGE was subjected to assays such as proliferation, cytotoxicity, Mitotracker, ATP production, and O₂ consumption rate as well as western blotting to demonstrate the expression of proteins related to mitochondria functions. The expression of hypoxia-inducible factor-1α (HIF-1α) was diminished utilizing siRNA transfection. Results: Brain samples from KRGE-administered mice harbored an increased number of GFAP-expressing astrocytes. KRGE triggered the proliferation of astrocytes in vitro. Enhanced mitochondrial biogenesis induced by KRGE was detected using Mitotracker staining, ATP production, and O₂ consumption rate assays. The expression of proteins related to mitochondrial electron transport was increased in KRGE-treated astrocytes. These effects were blocked by HIF-1α knockdown. The factors secreted from KRGE-treated astrocytes were determined, revealing the expression of various cytokines and growth factors, especially those related to angiogenesis and neurogenesis. KRGE-treated astrocyte conditioned media enhanced the differentiation of adult neural stem cells into mature neurons, increasing the migration of endothelial cells, and these effects were reduced in the background of HIF-1α knockdown. Conclusion: Our findings suggest that KRGE exhibits prophylactic potential by stimulating astrocyte mitochondrial biogenesis through HIF-1α, resulting in improved neurovascular function.