• YAKHAK HOEJI
• /
• 제49권2호
• /
• pp.168-173
• /
• 2005

Alzheimers disease (AD) is the most prevalent form of neurodegenerations associated with aging in the human population. This disease is characterized by the extracellular deposition of beta-amyloid (A ${\beta}$) peptide in cerebral plaques. The A ${\beta}$ peptide is derived from the ${\beta}$-amyloid precursor protein ( ${\beta}$APP). Photolytic processing of ${\beta}$APP by ${\beta}$-secretase(beta-site APP-cleaving enzyme, BASE) and ${\gamma}$-secretase generates the A ${\beta}$ peptide. Several lines of evidence support that A ${\beta}$-induced neuronal cell death is major mechanisms of development of AD. Accordingly, the ${\beta}$-and ${\gamma}$-secretase have been implicated to be excellent targets for the treatment of AD. We previously found that sesaminol glucosides have improving effect on memory functions through anti-oxidative mechanism. In this study, to elucidate possible other mechanism (inhibition of ${\beta}$-and ${\gamma}$-secretase) of sesaminol glucosides, we examined the improving effect of sesaminol glucosides in the scopolamine (1 mg/kg/mouse)-induced memory dysfunction using water maze test in the mice. Sesaminol glucosides (3.75, 7.5 mg/kg/6ml/day p.o., for 3 weeks) reversed the latency time, distance and velocity by scopolamine in dose dependent manner. Next, ${\beta}$-and ${\gamma}$-secretase activities were determined in different regions of brain. Sesaminol glucosides dose-dependently attenuated scopolamine-induced ${\beta}$-secretase activities in cortex and hippocampous and ${\gamma}$-secretase in cortex. This study therefore suggests that sesaminol glucosides may be a useful agent for prevention of the development or progression of AD, and its inhibitory effect on secretase may play a role in the improving action of sesaminol glucosides on memory function.

• Molecules and Cells
• /
• 제40권3호
• /
• pp.186-194
• /
• 2017

A brain-enriched secreting signal peptide, NELL2, has been suggested to play multiple roles in the development, survival, and activity of neurons in mammal. We investigated here a possible involvement of central NELL2 in regulating feeding behavior and metabolism. In situ hybridization and an immunohistochemical approach were used to determine expression of NELL2 as well as its colocalization with proopiomelanocortin (POMC) and neuropeptide Y (NPY) in the rat hypothalamus. To investigate the effect of NELL2 on feeding behavior, 2 nmole of antisense NELL2 oligodeoxynucleotide was administered into the lateral ventricle of adult male rat brains for 6 consecutive days, and changes in daily body weight, food, and water intake were monitored. Metabolic state-dependent NELL2 expression in the hypothalamus was tested in vivo using a fasting model. NELL2 was noticeably expressed in the hypothalamic nuclei controlling feeding behavior. Furthermore, all arcuatic POMC and NPY positive neurons produced NELL2. The NELL2 gene expression in the hypothalamus was up-regulated by fasting. However, NELL2 did not affect POMC and NPY gene expression in the hypothalamus. A blockade of NELL2 production in the hypothalamus led to a reduction in daily food intake, followed by a loss in body weight without a change in daily water intake in normal diet condition. NELL2 did not affect short-term hunger dependent appetite behavior. Our data suggests that hypothalamic NELL2 is associated with appetite behavior, and thus central NELL2 could be a new therapeutic target for obesity.

• Journal of Physiology & Pathology in Korean Medicine
• /
• 제21권4호
• /
• pp.1010-1016
• /
• 2007

Sagunjatang (Sagunja), containing Radix Astragali, Radix Ginseng, Fructus Schizandrae, Radix Ophiopogonis and Radix Glycyrrhizae, has been used as a prescription for ischemic heart and brain diseases in Korean traditional medicine. This study was designed to investigate the protective mechanisms of Sagunja on $H_2O_2$-induced cytotoxicity of H9c2 cardiomyocytes. Treatment with $H_2O_2$ resulted in death of H9c2 cells, characterized by apparent apoptotic features, including the fragmentation of nucleus and increase in sub-GO/G1fraction of cell cycle. However, Sagunja markedly suppressed the apoptotic characteristics of H9c2 cells induced by $H_2O_2$ with decrease of intracellular peroxide level. In addition, Sagunja suppressed the features of mitochondrial dysfunction, including change of mitochondrial membrane potential, in $H_2O_2$- treated cells. Additionally, Sagunja induced the expression of HO-1 protein in both time-and dose-dependent manner. The role of HO-1 in ROS-scavenging activity of Sagunja is proposed.

• The Korean Journal of Physiology and Pharmacology
• /
• 제10권5호
• /
• pp.235-242
• /
• 2006

Cortical malformation-associated epileptic seizures are resistant to conventional anticonvulsant drugs. Relatively little research has been conducted on the effects of antiepileptic drugs (AEDs) on seizure activity in a rat model of dysplasia. We have used rats exposed to methylazoxymethanol acetate (MAM) in utero, an animal model featuring nodular heterotopia, to investigate the effects of ethosuximide (ETX) in the dysplastic brain. Pilocarpine was used to induce acute seizure in MAM-exposed and age-matched vehicle-injected control animals. Field potential recordings were used to monitor the amplitude and number of population spikes, and paired pulse inhibition in response to stimulation of the commissural pathway. Pharmaco-resistance was tested by measuring seizure latencies after pilocarpine administration (320 mg/kg, Lp.) with and without pre-treatment with ETX. Pre-treatment with 300 mg of ETX significantly prolonged the latency to the status epilepticus (SE) in both control and MAM-treated groups. Pre-treatment with ETX 100mg and ETX 200 mg had little effect in MAMexposed rats. However, ETX 200 mg prolonged the latency to the SE in control groups. Spontaneous field potential and secondary after-discharges were higher for MAM-treated rat in comparison with control rats injects with ETX. The main findings of this study are that acute seizures initiated in MAM-exposed rats are relatively resistant to standard ETX assessed in vivo. These data suggest that ETX do not prolong seizure latencies in MAM-rats exposed to pilocarpine.

• The Korean Journal of Physiology and Pharmacology
• /
• 제22권3호
• /
• pp.301-309
• /
• 2018

Statins mediate vascular protection and reduce the prevalence of cardiovascular diseases. Recent work indicates that statins have anticonvulsive effects in the brain; however, little is known about the precise mechanism for its protective effect in kainic acid (KA)-induced seizures. Here, we investigated the protective effects of atorvastatin pretreatment on KA-induced neuroinflammation and hippocampal cell death. Mice were treated via intragastric administration of atorvastatin for 7 days, injected with KA, and then sacrificed after 24 h. We observed that atorvastatin pretreatment reduced KA-induced seizure activity, hippocampal cell death, and neuroinflammation. Atorvastatin pretreatment also inhibited KA-induced lipocalin-2 expression in the hippocampus and attenuated KA-induced hippocampal cyclooxygenase-2 expression and glial activation. Moreover, AKT phosphorylation in KA-treated hippocampus was inhibited by atorvastatin pretreatment. These findings suggest that atorvastatin pretreatment may protect hippocampal neurons during seizures by controlling lipocalin-2-associated neuroinflammation.

• Journal of Biomedical Engineering Research
• /
• 제29권1호
• /
• pp.73-81
• /
• 2008

The purpose of this study is to observe the brain activity patterns during visual oddball tasks with two difficulty levels by the analysis of high-density event-related potential (ERP). Along with conventional statistical analysis of averaged ERP waveforms, we applied independent component analysis (ICA) for the individual, single-trial analysis and verified its effectiveness. We could identify multiple ERP components such as early visual components (P1, N1), and two components which seem to be important task-related components and showed difficulty-dependent variability (P2, P300). The P2 was found around central region at $180{\sim}220ms$, and the P300 was found globally at $300{\sim}500ms$ poststimulus. As the task became difficult, the P2 amplitude increased, and the P300 amplitude decreased. After single-trial ERPs were decomposed into multiple independent components (ICs), several ICs resulting from P2 and P300 sources were identified. These ICs were projected onto scalp electrodes and the projected ICs were statistically compared according to two task difficulties. For most subjects, the results obtained from single-trial/individual analysis using ICA gave the tendencies of amplitude change that are similar to the averaged ERP analysis for most subjects. The temporal pattern and number of ICs corresponding to ${\mu}$ rhythm was not dependent on the task difficulty. It seems that the motor response was not affected by the task difficulty.

• The Journal of Korean Physical Therapy
• /
• 제26권6호
• /
• pp.436-441
• /
• 2014

Purpose: The objective of this study was to offer clinical primary data that it's aims to examine effects of transcranial direct current stimulation (tDCS) on cognitive function and biochemical change of rat with alzheimer's disease(AD) induced by injecting scopolamine. Methods: Subjects were instructed cognitive dysfunction model, rat of Sprague-Dawley system was injected with scopolamine and each experimental group was classified into three; group I (n=16) is non-treatment groups; group II (n=16) is applied with the tacrine; group III (n=16) is applied with the tDCS. The ziggurat task test was conducted to observe behavioral changes and cognitive function ability and 7, 14, 21, 28 days after the model. Acetylcholine Esterase (Ach E) activity was examined for biochemical assessment of which the results are followed. Results: Participants showed as to behavioral change, tacrine application group was the most significantly responded, following tDCS application group. As to biochemical change, same as above, tacrine application group was the most significantly responded, following tDCS application group. Conclusion: From these results, confirm that tDCS application to rat with alzheimer's disease leads to positive effects on behavioral, cognitive function changes, and biochemical changes, lasting for certain period of time. This study, in particular, tDCS, which can change excitability of brain cells non-invasively, could provide basic data that is useful as a new treatment way for the patients with cognitive dysfunction.

• Journal of Physiology & Pathology in Korean Medicine
• /
• 제20권6호
• /
• pp.1672-1677
• /
• 2006

Sarcodon aspratus is the mushroom of Telephoracea which was been classified into Alphllophorales. The aqueous extract of Sarcodon aspratus in known to have anti-tumor activity, immune modulatory effect, and anti-oxidative action. The descending pain control system consists of three major components: the periaqueductal gray (PAG) of the midbrain, the rostroventral medulla including the nucleus raphe magnus, and the spinal dorsal horn. Glutamate is the primary excitatory neurotransmitter in the brain. Glutamate ionotropic receptors are classified as N-methyl-D-aspartate (NMDA) receptor, ${\alpha}$-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor, and kainate receptor. In the present study, the modulation of Sarcodon aspratus on the ion currents activated by glutamate, NMDA, AMPA, and kainate in the acutely dissociated PAG neurons was investigated by nystatin-perforated patch-clamp technique under boltage-clamp condition. Sarcodon aspratus increased glutamate- and NMDA-induced ion currents were not increased by Sarcodon aspratus. The present results show that Sarcodon aspratus may activate the descending pain control system in rat PAG neurons through NMDA receptor.

• Biomolecules & Therapeutics
• /
• 제20권3호
• /
• pp.332-339
• /
• 2012

The components of Magnolia officinalis have well known to act anti-inflammatory, anti-oxidative and neuroprotective activities. These efficacies have been sold many products as nutritional supplement extracted from bark of Magnolia officinalis. Thus, to assess and compare neuroprotective effect in the nutritional supplement (Magnolia $Extract^{TM}$, Health Freedom Nutrition LLC, USA) and our ethanol extract of Magnolia officinalis (BioLand LTD, Korea), we investigated memorial improving and anti-Alzheimer's disease effects of extract products of Magnolia officinalis in a transgenic AD mice model. Oral pretreatment of two extract products of Magnolia officinalis (10 mg/kg/day in 0.05% ethanol) into drinking water for 3 months ameliorated memorial dysfunction and prevented $A{\beta}$ accumulation in the brain of Tg2576 mice. In addition, extract products of Magnolia officinalis also decreased expression of ${\beta}$-site APP cleaving enzyme 1 (BACE1), amyloid precursor protein (APP) and its product, C99. Although both two extract products of Magnolia officinalis could show preventive effect of memorial dysfunction and $A{\beta}$ accumulation, our ethanol extract of Magnolia officinalis (BioLand LTD, Korea) could be more effective than Magnolia $Extract^{TM}$ (Health Freedom Nutrition LLC, USA). Therefore, our results showed that extract products of Magnolia officinalis were effective for prevention and treatment of AD through memorial improving and anti-amyloidogenic effects via down-regulating ${\beta}$-secretase activity, and neuroprotective efficacy of Magnolia extracts could be differed by cultivating area and manufacturing methods.

• Korean Journal of Acupuncture
• /
• 제26권2호
• /
• pp.39-51
• /
• 2009

목적 : 신맥 혈위 자극이 뇌활성화 변화에 미치는 영향에 있어 자침 시술자간의 재현성을 fMRI 영상을 통해 평가하고자 하였다. 방법 : 본 연구는 건강한 성인 남자 15명을 대상으로 실시하였으며, 15명의 피험자 중 7명은 각각 2회 방문하였으며, 두 시술자에 의해 침을 맞고 총 4개의 데이터를 얻었다. 나머지 8명은 1회 방문하여 두 시술자에게 침을 맞아 2개씩의 데이터를 얻어 총 44개의 fMRI 데이터를 얻었다. 실험자간의 차이를 줄이기 위해 자침의 깊이와 회전, 강도 등을 동일하게 하였으며, 우측 신맥혈에 자침하였다. 침에 의해 활성화되는 영역을 확인하기 위해 블록디자인을 사용하여 fMRI를 촬영하였다. 결과 : 다른 날에 실시한 같은 시술자내의 재현성은 24 %, 같은 날 실시한 다른 시술자간의 재현성은 64 % 로, 다른 시술자간의 재현성이 서로 다른 날 실시한 같은 시술자내의 재현성보다 높게 나타났다. 결론 : 침을 이용한 fMRI의 실험에서 시술자에 의한 차이 외에도 실험하는 날짜의 차이, 피험자 인체의 생리적인 변화 등에 의한 차이가 크다는 것을 본 실험을 통하여 확인하였다. 그리고 자침의 깊이와 회전, 자극의강도 등을 동일하게 함으로써 다른 시술자간의 재현성을 높일 수 있다는 것을 확인했다. 추후 침실험에 있어서 여러 변수들에 의한 차이를 극복하고 재현성을 높일 수 있는 방법에 관한 더욱 심도 있는 연구가 필요하다.