• Clinical and Experimental Pediatrics
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• 제57권3호
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• pp.101-109
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• 2014

The use of glucocorticoids (GCs) in the perinatal period is suspected of being associated with adverse effects on long-term neurodevelopmental outcomes for preterm infants. Repeated administration of antenatal GCs to mothers at risk of preterm birth may adversely affect fetal growth and head circumference. Fetal exposure to excess GCs during critical periods of brain development may profoundly modify the limbic system (primarily the hippocampus), resulting in long-term effects on cognition, behavior, memory, co-ordination of the autonomic nervous system, and regulation of the endocrine system later in adult life. Postnatal GC treatment for chronic lung disease in premature infants, particularly involving the use of dexamethasone, has been shown to induce neurodevelopmental impairment and increases the risk of cerebral palsy. In contrast to studies involving postnatal dexamethasone, long-term follow-up studies for hydrocortisone therapy have not revealed adverse effects on neurodevelopmental outcomes. In experimental studies on animals, GCs has been shown to impair neurogenesis, and induce neuronal apoptosis in the immature brains of newborn animals. A recent study has demonstrated that dexamethasone-induced hypomyelination may result from the apoptotic degeneration of oligodendrocyte progenitors in the immature brain. Thus, based on clinical and experimental studies, there is enough evidence to advice caution regarding the use of GCs in the perinatal period; and moreover, the potential long-term effects of GCs on brain development need to be determined.

• Nutrition Research and Practice
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• 제11권1호
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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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• 제19권1호
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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.

• 고려인삼학회:학술대회논문집
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• 고려인삼학회 2002년도 학술대회지
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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.

• 생명과학회지
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• 제26권1호
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• pp.8-16
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• 2016

적절한 농도의 활성산소종(ROS)은 병원체에 대한 세포의 방어, 신호 전달, 세포 성장 및 유전자 발현을 포함한 다양한 정상 세포 기능을 매개한다. 최근의 연구는 ROS와 ROS를 생성하는 NADPH 산화 효소(Nox)가 성인 쥐 뇌의 뇌실 하 영역(SVZ)에 있는 신경 줄기세포의 자가 복제와 신경 세포 분화에 중요하다는 것을 보여 주었다. 본 연구에서 세포 내 ROS가 갓 태어난 쥐의 뇌에서 적출되어 배양된 SVZ 신경 줄기세포에서 검출된 것으로 나타났다. Nox 유사 유전자들 중 Nox4가 배양된 세포에서 주로 발현되었고, Nox1과 Nox2는 거의 발현되지 않았다. 또한, Nox4 유전자는 신경 세포 분화 동안 최대 10배까지 발현이 크게 증가하였다. Immunocytochemistry결과 Nox4 단백질은 신경 세포 특이적인 tubulin인 Tuj1-양성 신경 세포에서 주로 발견되었다. 이와 맥을 같이 하여, 내인성 ROS는 분화 후 축삭돌기를 가지고 있으며 신경 세포로 보이는 세포에서만 검출되었다. 또한, ROS를 제거하는N-acetyl cysteine에 의해 세포 산화 환원 상태가 교란되었을 때, 신경 세포로의 분화가 크게 감소하였다. 마지막으로, shRNA를 이용하 여 Nox4를 knockdown한 세포에서 신경 세포로의 분화가 감소하였다. 이러한 연구 결과는 Nox4가 갓 태어난 쥐의 SVZ 신경 줄기 세포의 주요한 ROS 생성 효소이고, Nox4에 의한 ROS생성이 신경 세포 분화에 중요하다는 것을 암시한다.

• BMB Reports
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• 제44권12호
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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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• 제46권3호
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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.

• Anatomy and Cell Biology
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• 제56권1호
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• pp.69-85
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• 2023

Depression is one of the most common neuropsychiatric disorders and is associated with dysfunction of the neuroendocrine system and alterations in specific brain proteins. Boophone disticha (BD) is an indigenous psychoactive bulb that belongs to the Amaryllidacae family, which is widely used in Southern Africa to treat depression, with scientific evidence of potent antidepressant-like effects. The present study examined the antidepressant effects of BD and its mechanisms of action by measuring some behavioural parameters in the elevated plus maze, brain content of corticosterone, brain derived neurotropic factor (BDNF), and neuroblast differentiation in the hippocampus of Balb/c mice exposed to the five day repeated forced swim stress (5d-RFSS). Male Balb/c mice were subjected to the 5d-RFSS protocol to induce depressive-like behaviour (decreased swimming, increased floating, decreased open arm entry, decreased time spent in the open arms and decreased head dips in the elevated plus maze test) and treated with distilled water, fluoxetine and BD. BD treatment (10 mg/kg/p.o for 3 weeks) significantly attenuated the 5d-RFSS-induced behavioural abnormalities and the elevated serum corticosterone levels observed in stressed mice. Additionally, 5d-RFSS exposure significantly decreased the number of neuroblasts in the hippocampus and BDNF levels in the brain of Balb/c mice, while fluoxetine and BD treatment attenuated these changes. The antidepressant effects of BD were comparable to those of fluoxetine, but unlike fluoxetine, BD did not show any anxiogenic effects, suggesting better pharmacological functions. In conclusion, our study shows that BD exerted antidepressant-like effects in 5d-RFSS mice, mediated in part by normalizing brain corticosterone and BDNF levels.