• Journal of Physiology & Pathology in Korean Medicine
• /
• v.27 no.1
• /
• pp.57-62
• /
• 2013

Alzheimer's disease (AD), one of the most common forms of dementia, is characterized pathologically by the presence of intracellular neurofibrillary tangles and deposition of ${\beta}$-amyloid ($A{\beta}$) peptides of 40-42 residues, which are generated by processing of amyloid precursor protein (APP). $A{\beta}$ has been believed to be neurotoxic and now is also considered to have a role on the mechanism of memory dysfunction. Here, we show that MeOH extract from stem bark of Platycarya strobilacea Sieb. et. Zucc. (PSM) affects on the processing of APP from the APPswe over-expressing Neuro2a cell line. We found that PSM may regulate the processing of APP and increase the sAPP${\alpha}$. PSM does not change the protein level of presenilin and nicastrin, however, it reduces the protein expression level of BACE1. In addition, PSM reduces the secretion level of $A{\beta}42$ and $A{\beta}40$ from the cell line without toxicity. We suggest that Platycarya strobilacea may be useful as a herbal medicine to treat Alzheimer's disease.

• Journal of Life Science
• /
• v.29 no.7
• /
• pp.817-823
• /
• 2019

Immune system provides defense integrity of body against external invaders. In order to accomplish the important defending role immune system is composed of many different components which are regenerated continuously during lifespan. The key components are professional killing cells such as macrophage, neutrophil, natural killer cell, and cytotoxic T cell and professional blocking molecule, antibody, which is produced by plasma cell, the terminal differentiated B cell. Immune response is orchestrated harmoniously by all these components mediated through antigen presenting cells such as dendritic cells. Immune responses can be divided into two ways: innate immune response and adaptive immune response depending on induction mechanism. Aging is a broad spectrum of physiological changes. Likewise other physiological changes, the immune components and responses are wane as aging is progressing. Immune responses become decline and dysregulating, which is called immunosenescense. Immune components of both innate and adaptive immune response are affected as aging progresses leading to increased vulnerability to infectious diseases. Numbers of immune cells and amounts of soluble immune factors were decreased in aged animal models and human and also functional and structural alterations in immune system were reduced and declined. Cellular intrinsic changes were discovered as well. Recent researches focusing on aging have been enormously growing. Many advanced tools were developed to bisect aging process in multi-directions including immune system area. This review will provide a broad overview of aging-associated changes of key components of immunity.

• Journal of Oriental Neuropsychiatry
• /
• v.21 no.2
• /
• pp.125-140
• /
• 2010

Objectives : The purpose of this study is to examine from various angles the protective effect of Gastrodia elata Blume (GEB) against nerve cell death induced by $\beta$-amyloid by using the cell line SH-SY5Y, which is commonly utilized for toxicity testing in nerve cells, and to find out its mechanism of action. Methods : To begin with, as a result of assessing the rate of cell survival by employing MTT reduction assay, the treatment with $\beta$-amyloid at different concentrations caused cytotoxicity, which was inhibited by preprocessing GEB extract. In addition, after $\beta$-amyloid was processed with the cell SH-SY5Y, apoptosis progressed, which was reduced effectively by processing GEB extract. Results : When cytotoxicity was caused by using hydrogen peroxide, a representative ROS, in order to examine the antioxidant effect of GEB, its protective effect was also observed. Apart from ROS, reactive nitrogen species (RNS) are also known to play a crucial role in nerve cell death. The treatment with the NO donor SNAP increased the production of nitric oxide and the expression of iNOS, which was also inhibited by GEB extract. Meanwhile, as an attempt to find out the mechanism of action explaining the antioxidant effect, the intracellular antioxidant enzyme expressions were measured by RT-PCR, which showed that GEB extract increased the expressions of heme oxygenase-1, GAPDH and $\gamma$-glutamate cysteine ligase. Lastly, GEB extract had a protective effect against impaired memory induced by scopolamine in animal models (in vivo). Conclusions : These findings indicate that GEB has a protective effect against the death of cranial nerve cells, suggesting possibilities for the prevention and treatment of AD.

• Journal of the Institute of Electronics Engineers of Korea TC
• /
• v.41 no.9
• /
• pp.73-80
• /
• 2004

In this paper, we present the cell resequencing buffer to solve the cell sequence integrity problem of the Cyclic banyan network that is a high-performance fault-tolerant cell switch. By offering multiple paths between input ports and output ports, using the deflection self-routing, the Cyclic banyan switch offer high reliability, and it also solves congestion problem for the internal links of the switch. By the way, these multiple paths can be different lengths for each other. Therefore, the cells departing from an identical source port and arriving at an identical destination port can reach to the output port as the order that is different from the order arriving at input port. The proposed cell resequencing buffer is a hardware sliding window mechanism. to solve such cell sequence integrity problem. To calculate the size of sliding window that cause the prime cost of the presented device, we analyzed the distribution of the cell delay through the simulation analyses under traffic load that have a nonuniform address distribution that express tile Property of traffic of the Internet. Through these analyses, we found out that we can make a cell resequencing buffer by which the cell sequence integrity is to be secured, by using a, few of ordinary memory and control logic. The cell resequencing buffer presented in this paper can be used for other multiple paths switching networks.

• Hanyang Medical Reviews
• /
• v.33 no.1
• /
• pp.10-16
• /
• 2013

Follicular helper T cells (Tfh) play a significant role in providing T cell help to B cells during the germinal center reaction, where somatic hypermutation, affinity maturation, isotype class switching, and the differentiation of memory B cells and long-lived plasma cells occur. Antigen-specific T cells with IL-6 and IL-21 upregulate CXCR5, which is required for the migration of T cells into B cell follicles, where these T cells mature into Tfh. The surface markers including PD-1, ICOS, and CD40L play a significant role in providing T cell help to B cells. The upregulation of transcription factor Bcl-6 induces the expression of CXCR5, which is an important factor for Tfh differentiation, by inhibiting the expression of other lineage-specific transcription factors such as T-bet, GATA3, and RORγt. Surprisingly, recent evidence suggests that CD4 T cells already committed to Th1, Th2, and Th17 cells obtain flexibility in their differentiation programs by downregulating T-bet, GATA3, and RORγt, upregulating Bcl-6 and thus convert into Tfh. Limiting the numbers of Tfh within germinal centers is important in the regulation of the autoantibody production that is central to autoimmune diseases. Recently, it was revealed that the germinal center reaction and the size of the Tfh population are also regulated by thymus-derived follicular regulatory T cells (Tfr) expressing CXCR5 and Foxp3. Dysregulation of Tfh appears to be a pathogenic cause of autoimmune disease suggesting that tight regulation of Tfh and germinal center reaction by Tfr is essential for maintaining immune tolerance. Therefore, the balance between Tfh and Tfr appears to be a critical peripheral tolerance mechanism that can inhibit autoimmune disorders.

• Proceedings of the Korean Society of Applied Pharmacology
• /
• 2008.04a
• /
• pp.33-45
• /
• 2008

Auditory fear memory is thought to be maintained by fear conditioning-induced potentiation of synaptic efficacy. The conditioning-induced potentiation has been shown to be maintained, at least in part, by enhanced expression of surface AMPA receptor (AMPAR) at excitatory synapses in the lateral amygdala (LA). Depotentiation, reversal of conditioning-induced potentiation, has been proposed as a cellular mechanism for fear extinction. However, a direct link between depotentiation and extinction has not yet been tested. To address this, we applied both ex vivo and in vivo approaches to rats in which fear memory had been consolidated. We found a novel form of ex vivo depotentiation; the depotentiation reversed conditioning-induced potentiation at thalamic input synapses onto the LA (T-LA synapses) ex vivo, and it could be induced only when both NMDA and metabotropic glutamate receptors were co-activated. Extinction returned the enhanced T-LA synaptic efficacy observed in conditioned rats to baseline and occluded the depotentiation. Consistently, extinction reversed conditioning-induced enhancement of surface expression of AMPAR subunits in LA synaptosomal preparations. A GluR2-derived peptide that blocks regulated AMPAR endocytosis inhibited depotentiation, and microinjection of a cell-permeable form of the peptide into the LA attenuated extinction. Our results are consistent with the use of depotentiation to weaken potentiated synaptic inputs onto the LA during extinction, and they provide strong evidence that AMPAR removal at excitatory synapses in the LA underlies extinction. The results described here are in line with previous findings. Neural activity in the LA has been shown to decrease after extinction in the rat and human. The NMDAR dependency of the depotentiation fits nicely with a large body of evidence that fear extinction depends upon amygdala NMDARs. Similarly, blockade of metabotropic glutamate recepotrs in the LA has recently been shown to attenuate fear extinction.

• Korean Journal of Biological Psychiatry
• /
• v.5 no.1
• /
• pp.83-94
• /
• 1998

Objectives : Phencyclidine(PCP) or PCP-like substances such as ketamine have been known to rekindle the cognitive dysfunction in schizophrenia. The aims of this study were to identify whether PCP-like substances can produce cognitive deficit in schizophrenia, to discuss relation with aging process, and finally to speculate underlying neurochemical mecha-nisms by various drug responses. Methods : In experiment I, radial maze tests were done in 24 Sprague-Dawley rats for 3 days to get baseline data. Being divided into 4 groups(6 rats respectively) of normal aged, normal adult controls, atropine-treated and ketamine-treated, the radial maze tests were repeated on every week for 6 weeks, and then the rats were sacrificed by intracardiac perfusion with phosphate-buffered 10% formaldehyde solution for histology. The brain specimen was stained with hematoxylin-eosin to count cells in the prefrontal cortex and hippocampus. In experiment II, radial maze tests were done for 48 rats before any drug treatment and only after ketamine administration. Thereafter, haloperidol, bromocriptine, clonidine, nimodipine, tacrine, valproic acid, naloxone and fluoxetine were intramuscularly injected on every other day in addition to ketamine. Radial maze tests were repeated on every week for 6 weeks, and then rats were prepared by the same procedure for histology. Results : 1) Reaction times of radial maze tests of atropine-treated rats were significantly prolonged than those of normal aged(p<0.05) or normal adult controls(p<0.05). Cell numbers of prefrontal cortex & hippocampus in ketamine-treated rats were significantly reduced than those in normal aged (p<0.05) or normal adult controls(p<0.005). 2) Reduced cell numbers by ketamine became significantly raised by tacrine administration in prefrontal cortex & hippocampus(p<0.05), while there were no significant changes on radial maze tests. Cell numbers also tended to be raised by nimodipine, fluoxetine and haloperidol administration. Conclusions : In conclusion, the visuospatial memory disorders in ketamine-induced psychotic rats might be partly asso-ciated with aging process. Furthermore, the responses to the various drugs suggested cholinergic system might have an important role in the neurochemical mechanism of the cognitive dysfunction in ketamine-induced psychosis. Otherwise, calcium metabolism as well as serotonergic and dopaminergic systems seemed to be possibly related.

• Journal of Korea Multimedia Society
• /
• v.10 no.4
• /
• pp.462-469
• /
• 2007

ATM protocol has the techniques such as cell discarding priority, traffic shaping and traffic policing. ATM based MPLS(Multiprotocol Label Switching) is discussed for its provisioning QoS commitment capabilities, traffic engineering and smooth migration for BcN using conventional ATM infra in Korea. This paper proposes preventive congestion control mechanism for detecting HTR(Hard To Reach) LSP(Label Switched Path) in ATM based MPLS systems. In particular, we decide HTR LSP using real time signaling information(etc., PTI,AIS/RDI) for applying HTR concept in circuit switching to ATM based MPLS systems and use those session gap and percentage based control algorithm that were used in conventional PSTN call controls. We concluded that it maximized the efficiency of network resources by restricting ineffective machine attempts. Proposed control can handle 208% call processing and more than 147% success call, than those without control. It can handle 187% BHCA(Busy Hour Call Attempts) with 100 times less than use of exchange memory.

• The Korean Journal of Physiology and Pharmacology
• /
• v.6 no.3
• /
• pp.143-147
• /
• 2002

Granule cells in dentate gyrus of hippocampus relay information from entorhinal cortex via perforant fiber to pyramidal cells in CA3 region. Their electrical activities are known to be closely associated with seizure activity as well as memory acquisition. Since action potential is a stereotypic phenomena which is based on all-or-none principle of $Na^+$ current, the neuronal firing pattern is mostly dependent on afterpotentials which follows the stereotypic $Na^+$ spike. Granule cells in dentate gyrus show afterdepolarization (ADP), while interneurons in dentate gyrus have afterhyperpolarizaton. In the present study, we investigated the ionic mechanism of afterdepolarization in hippocampal dentate granule cell. Action potential of dentate granule cells showed afterdepolarization, which was characterized by a sharp notch followed by a depolarizing hump starting at about $-49.04{\pm}1.69\;mV\;(n=43,\;mean{\pm}SD)$ and lasting $3{\sim}7$ ms. Increase of extracellular $Ca^{2+}$ from 2 mM to 10 mM significantly enhanced the ADP both in amplitude and in duration. A $K^+$ channel blocker, 4-aminopyridine (4-AP, 2 mM), enhanced the ADP and often induced burst firings. These effects of 10 mM $Ca^{2+}$ and 4-AP were additive. On the contrary, the ADP was significantly suppressed by removal of external $Ca^{2+},$ even in the presence of 4-AP (2 mM). A $Na^+$ channel blocker, TTX (100 nM), did not affect the ADP. From these results, it is concluded that the extracellular $Ca^{2+}$ influx contributes to the generation of ADP in granule cells.

• Biomolecules & Therapeutics
• /
• v.32 no.1
• /
• pp.77-83
• /
• 2024

Alzheimer's disease (AD) is a neurodegenerative disease characterized by neuronal cell death and memory impairment. Corticosterone (CORT) is a glucocorticoid hormone produced by the hypothalamic-pituitary-adrenal axis in response to a stressful condition. Excessive stress and high CORT levels are known to cause neurotoxicity and aggravate various diseases, whereas mild stress and low CORT levels exert beneficial actions under pathophysiological conditions. However, the effects of mild stress on AD have not been clearly elucidated yet. In this study, the effects of low (3 and 30 nM) CORT concentration on Aβ_25-35-induced neurotoxicity in SH-SY5Y cells and underlying molecular mechanisms have been investigated. Cytotoxicity caused by Aβ_25-35 was significantly inhibited by the low concentration of CORT treatment in the cells. Furthermore, CORT pretreatment significantly reduced Aβ_25-35-mediated pro-apoptotic signals, such as increased Bim/Bcl-2 ratio and caspase-3 cleavage. Moreover, low concentration of CORT treatment inhibited the Aβ_25-35-induced cyclooxygenase-2 and pro-inflammatory cytokine expressions, including tumor necrosis factor-α and interleukin-1β. Aβ_25-35 resulted in intracellular accumulation of reactive oxygen species and lipid peroxidation, which were effectively reduced by the low CORT concentration. As a molecular mechanism, low CORT concentration activated the nuclear factor-erythroid 2-related factor 2, a redox-sensitive transcription factor mediating cellular defense and upregulating the expression of antioxidant enzymes, such as NAD(P)H:quinone oxidoreductase, glutamylcysteine synthetase, and manganese superoxide dismutase. These findings suggest that low CORT concentration exerts protective actions against Aβ_25-35-induced neurotoxicity and might be used to treat and/or prevent AD.