• International Journal of Oral Biology
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• v.49 no.1
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• pp.10-17
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• 2024

Glutamate-mediated oxidative stress causes neuronal cell death by increasing intracellular Ca²⁺ uptake, reactive oxidative species (ROS) generation, mitogen-activated protein kinase (MAPK) activation, and translocation of apoptosis-inducing factor (AIF) to the nucleus. In the current study, we demonstrated that corydaline exerts potent neuroprotective effects against glutamate-induced neurotoxicity. Treatment with 5 mmol/L glutamate increased cellular Ca²⁺ influx, ROS generation, MAPK activation, and AIF translocation. In contrast, corydaline treatment decreased cellular Ca²⁺ influx and ROS generation. Western blot analysis revealed that glutamate-mediated MAPK activation was attenuated by corydaline treatment. We further demonstrated that corydaline treatment inhibited the glutamate-mediated translocation of AIF to the nucleus. We propose that corydaline is a promising lead structure for the development of safe and effective neuroprotectants.

• The Korean Journal of Physiology and Pharmacology
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• v.16 no.1
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• pp.17-24
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• 2012

The hypothalamus-pituitary-adrenocortex (HPA) axis is the central mediator of the stress response. The supramammillary (SuM) region is relatively unique among the hypothalamic structures in that it sends a large, direct projection to the hippocampal formation. It has been shown that mild stress could activate the SuM cells that project to the hippocampus. However, the role of these cell populations in modulating the stress response is not known. The present study examined the effect of stress on different populations of SuM cells that project to the hippocampus by injecting the fluorescent retrograde tracer, fluorogold (FG), into the hippocampus and utilizing the immunohistochemistry of choline acetyltransferase (ChAT), corticotrophin releasing factor (CRF), serotonin (5-HT), glutamate decarboxylase (GAD), tyrosine hydroxylase (TH) and NADPH-d reactivity. Immobilization (IMO) stress (2 hr) produced an increase in the expression of ChAT- immunoreactivity, and tended to increase in CRF, 5-HT, GAD, TH-immunoreactivity and nitric oxide (NO)-reactivity in the SuM cells. Fifty-three percent of 5-HT, 31% of ChAT and 56% of CRF cells were double stained with retrograde cells from the hippocampus. By contrast, a few retrogradely labeled cells projecting to the hippocampus were immunoreactive for dopamine, ${\gamma}$-aminobutyric acid (GABA) and NO. These results suggest that the SuM region contains distinct cell populations that differentially respond to stress. In addition, the findings suggest that serotonergic, cholinergic and corticotropin releasing cells projecting to the hippocampus within the SuM nucleus may play an important role in modulating stress-related behaviors.

• Journal of electromagnetic engineering and science
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• v.15 no.3
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• pp.173-180
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• 2015

To explore the effects of radiofrequency electromagnetic field on the fate of neuronal cells, we investigated whether exposure to 915 MHz radiofrequency identification (RFID) caused morphological changes in neuronal cells in rat hippocampal dentate gyrus (DG). A reverberation chamber was used as a whole-body RFID exposure system. Rats were assigned to two groups: sham- and RFID-exposed groups. Rats in the RFID-exposed group were exposed to RFID at 4 W/kg specific absorption rate (SAR) for 8 hours daily, 5 days per week, for 2 weeks. Morphological evaluation of DG was performed using immunohistochemistry with doublecortin (DCX) as a neuronal precursor cell marker and neuronal nuclei (NeuN) as a mature neuronal cell marker. No significant morphological changes in DCX+ or NeuN+ cells in the DG of RFID-exposed rats were observed. These results suggest that RFID exposure induces no significant change in DCX+ neuronal precursor or NeuN+ neuronal cells in DG of rats.

• Journal of Ginseng Research
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• v.31 no.1
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• pp.44-50
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• 2007

Ginseng powerfully tonifies the original Qi. Ginseng used for insomnia, palpitations with anxiety, restlessness from deficient Qi and blood and mental disorientation. In order to investigate whether Ginseng cerebral ischemia-induced neuronal and cognitive impairments, we examined the effect of Ginseng on ischemia-induced cell death in the hippocampus, and on the impaired learning and memory in the Morris water maze and passive avoidance in rats. Ginseng when administered to rat at a dose of 200 mg/kg i.p. water extracts to 0 minutes and 90 minutes after 4-VO, significantly neuroprotective effects by 86.4% in the hippocampus of treated rats. For behavior test, rats were administered Ginseng (200mg/kg p.o.) daily for two weeks, followed by their training to the tasks. Treatment with Ginseng produced a marked improvement in escape latency to find the platform in the Morris water maze. Ginseng reduced the ischemia-induced learning disability in the passive avoidance. Consistent with behavioral data, treatments with Ginseng reduced jschemia-induced cell death in the hippocampal CA1 area. Oxidative stress is a causal factor in the neuropathogenesis of ischemic-reperfusion injury. Oxidative stress was examined in a rat model of global brain ischemia. The effects of Ginseng on lipid peroxidation (inhibition of the production of malondialdehyde, MDA) in different regions of the rat brain were studied. Ferrous sulfate and ascorbic acid (FeAs) were used to induce lipid peroxidation. The antiperoxidative effect showed 48-72% protection from tissue damage as compared with untreated animals. These results showed that Ginseng have a protective effect against ischemia-induced neuronal loss and learning and memory damage.

• Journal of Physiology & Pathology in Korean Medicine
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• v.16 no.3
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• pp.594-601
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• 2002

The current study was carried out to evaluate neuroprotective effects of Citri Pericarpium after transient global ischemia in gerbils. Male Mongolian gerbils weighing 60-80g were anesthetized with 2% isoflurane mixed with 30% oxygen and 70 % nitrogen. Bilateral common carotid arteries were occluded for 5 minute with microaneurysm dips. On 3 or 7 days after ischemic surgery, the gerbils were sacrificed. The brain were removed, embedded in paraffin and sectioned at 8㎛-thickness. Gerbils that received ischemic insult for 5 min showed extensive neuronal damage in the hippocampal CA1 region, and the number of viable neuronal cell was 51.0±2.5/mm, 32.2% of normal group at 7 days after ischemic surgery. In animals that underwent the extract of Citri Pericarpium treatment, the number of viable neuronal cell were significantly better preserved at 110.58±3.58/mm, 72.0% of normal group than those of ischemic group (P<0.01). In the immunohistochemistry of Bax and Bcl-2, the Citri Pericarpium treated group down-regulated the expression of Bax protein at 72hr after transient global ischemia. In contrast, Bcl-2 protein level was not changed. The appearance in TUNEL assay is similar to the pattern of Bax protein. The water extract of Citri Pericarpium significantly reduced the number of TUNEL-positive CA1 pyramidal neurons at 72hr. The results suggest that Citri Pericarpium has potential neuroprotective effects in the transient global ischemia and the increase in the ratio of Bcl-2 to Bax may contribute to the anti-apoptotic effect of Citri Pericarpium.

• Journal of Sasang Constitutional Medicine
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• v.26 no.2
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• pp.165-179
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• 2014

Objectives To evaluate the neuroprotective effects of Hyangsayangwi-tang (HY), a Korean traditional medicinal prescription in a Parkinson's disease mouse model. Methods Four groups(each of 10 mouse per group) were used in this study. The neuroprotective effect of HY was examined in a Parkinson's disease mouse model. C57BL/6 mouse treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 30mg/kg/day), intraperitoneal (i.p.) for 5 days. Slow behavioral responses and memory disorder is the major clinical symptoms of PD. In order to investigate the effect of HY on recovery of behavioral deficits and memory, we examined the motor function and memory by using Morris water maze and Forced swimming test. Ischemic mouse brain stained with TTC(2,3,5 triphenyl tetrazolium chloride) in the MPTP-induced Parkinson's disease to find out ischemia and tissue damage in mouse. The convenient, simple, and accurate high-performance liquid chromatography (HPLC) method was established for simultaneous determination of neurotransmitters in MPTP-HY group. To measure the amount of dopamine in mice brain, striatum-substantia nigra, was examined by Bradford assay. Immunohistochemistry was examined in the MPTP-induced Parkinson's disease (PD) mouse to evaluate the neuroprotective effects of Hyangsayangwi-tang on hippocampal lesion, ST and SNpc. Results and Conclusions Hyangsayangwi-tang (HY) prevents MPTP-induced loss of serotonin, hippocampus and TH-ir cell.

• The Journal of Korean Medicine
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• v.30 no.3
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• pp.1-14
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• 2009

Objectives : Alzheimer's disease (AD) is characterized by neuronal loss and extracellular senile plaque. Moreover, the cellular actions of ${\beta}$-amyloid (A${\beta}$ play a causative role in the pathogenesis of AD. This study was designed to determine whether Woo-Gui-Um, a commonly used Korean herbal medicine, has the ability to protect cortical and hippocampal neurons against A${\beta}_{25-35}$ neurotoxicity Methods : In the present study, the authors investigated the preventative effects of the water extract of Woo-Gui-Um in a mouse model of AD. Memory impairment was induced by intraventricularly (i.c.v.) injecting A${\beta}_{25-35}$ peptides into mice. Woo-Gui-Um extract was then administered orally (p.o.) for 14 days. In addition, A${\beta}_{25-35}$ toxicity on the hippocampus was assessed immunohistochemically, by staining for Tau, MAP2, TUNEL, and Bax, and by performing an in vitro study in PC12 cells. Results : Woo-Gui-Um extract had an effect to improve learning ability and memory score in the water maze task. Woo-Gui-Um extract had significant neuroprotective effects in vivo against oxidative damage and apoptotic cell death of hippocampal neurons caused by i.c.v. A${\beta}_{25-35}$. In addition, Woo-Gui-Um extract was found to have a protective effect on A${\beta}_{25-35}$-induced apoptosis, and to promote neurite outgrowth of nerve growth factor (NGF)-differentiated PC12 cells. Conclusions : These results suggest that Woo-Gui-Um extract reduces memory impairment and Alzheimer's dementia via an anti-apoptotic effect and by regulating Tau and MAP2 in the hippocampus.

• Journal of Life Science
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• v.30 no.6
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• pp.513-521
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• 2020

B-cell-specific Moloney murine leukemia virus integration site 1 (Bmi1) is a polycomb group protein and a core component of polycomb repressive complex 1. Initial research into Bmi1 has focused on its role in tumorigenesis, and it is generally accepted that it is important for the proliferation and survival of cancer cells. However, more recent studies have revealed that Bmi1 is downregulated in brains with neurodegenerative disease and that it regulates the function of mitochondria and reactive oxygen species levels. In this study, we tested the therapeutic potential of Bmi1 in pilocarpine-induced seizures in Bmi1-knockout mice. Bmi1 expression transiently increased in the hippocampal CA1 and CA3 and the dentate gyrus following pilocarpine-induced status epilepticus (SE). In terms of seizure behavior, SE induction was 43.14% and 53.57% for Bmi1^+/+ and Bmi1^+/- mice, respectively. However, there was no significant difference in mortality or hippocampal damage between the two groups. Two months after SE induction, the frequency of epileptic seizures in the Bmi1^+/- mice was 50% lower than in the control group, although the difference was not statistically significant. In addition, mossy fiber outgrowth in the Bmi1^+/- mice was significantly higher than in their wild-type littermates. Taken together, these data indicate that reduced Bmi1 activity increases pilocarpine-induced seizure probability and mossy fiber outgrowth.

• Journal of Acupuncture Research
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• v.33 no.4
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• pp.49-63
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• 2016

Objectives : This research was performed to investigate the effects of Jodeungsan pharmacopuncture(PA-J) of focal brain ischemia induced by middle cerebral artery occlusion(MCAO) in rats. Methods : The subjects were divided into 4 groups : control, acupuncture, pharmacopuncture PA-J1(11.43 mg / 250 g / $40{\mu}{\ell}$) and pharmacopuncture PA-J2(2.29 mg / 250 g / $40{\mu}{\ell}$). The focal brain ischemia was induced by intraluminal filament insertion into the middle cerebral artery. After 3 days of MCAO, Jodeungsan pharmacopuncture treatment was performed on the GB20, and the day after being treated with pharmacopuncture, the Morris water maze test was carried out on the assigned group. The series of processes were administered 6 times. Thereafter mGluR5, density of neuronal cell and ChAT were measured. Results : The results were as follows. 1. The distance to target significantly decreased in the 2nd trial of the Acu group on the water maze test for short-term memory. 2. The distance to target significantly decreased in the 4th trial of the PA-J2 group on the water maze test for long-term memory. 3. The intensity of mGluR5 significantly increased in the PA-J1 group compared with the control group. 4. The neuroprotective effect on the hippocampal CA1 significantly increased in the PA-J1 and PA-J2 groups compared with the control group. 5. The density of ChAT in the hippocampal CA1 significantly increased in the PA-J1 and PA-J2 groups compared with the control group. Conclusion : These results suggest that Jodeungsan pharmacopuncture may improve memory and cognitive impairment and also have neuroprotective effects on focal brain ischemia.

• Journal of Life Science
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• v.18 no.12
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• pp.1631-1636
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• 2008

Rhei Rhizoma (RR; 大黃) consists of the underground parts (rhizome and root) of Rheum officinale Baill. and Rheum palmatum L. (Polygonaceae), and is widely used in Southeast Asian folk medicine to alleviate liver and kidney damages. In this study, we investigated into the efficacy and mechanism of RR water extract in supporting neuronal survival in a hypoxia model of cultured rat hippocampal neurons. RR exhibited no cytotoxicity up to 10 ${\mu}g$/ml and exhibited neurosupportive effects at 2.5 ${\mu}g$/ml in normoxia. When RR was added to the culture media on 10 days in vitro (DIV10) and given a hypoxic shock (2% $O_2$/5% $CO_2$, 3 hr, $37^{\circ}C$) on DIV13, RR exhibited neuroprotective effects on 5 days post-shock. $H_2DCF$ stainings indicated that RR effectively prevents ROS production in both normoxia and hypoxia. JC-1 stainings showed that RR prevents dissipation of MMP in hypoxia. These results indicate that RR protects neurons by suppressing ROS production and MMP loss.