• 정신신체의학
• /
• 제20권2호
• /
• pp.135-138
• /
• 2012

기능성 위장관 장애(functional gastrointestinal disorder, FGID)의 생물학적 병태생리는 아직 명확하지 않은 실정이나 최근에 뇌-장관 축(brain-gut axis, BGA) 모델이 각광받고 있다. BGA 모델은 중추신경계(CNS)와 장관신경계(ENS)가 신경계, 신경내분비계, 신경면역계 등으로 밀접하게 연계되어 양방향성으로 항상성을 유지한다는 이론이다. 또한 BGA는 FGID에 대한 항우울제 효과의 이론적 근거를 제공한다. 저자들은 세로토닌 노르에프네프린 재흡수 차단제인 duloxetine이 목 이물감, 우울감을 보이는 환자와 상부 위장관 팽만감, 건강염려증적 불안을 보이는 환자에서 위장관 증상 및 정신의학적 증상에 효과적이었음을 경험하였다. 이에 두 증례보고를 통하여 BGA에 대해서 간략히 검토하고 duloxetine의 효과를 BGA의 측면에서 고찰하였다. 이 두 증례에서 duloxetine의 장관에서 뇌로의 영향(bottom-up regulation)으로는 세로토닌 수용체, 노르에피네프린 수용체 그리고 부신피질자극호르몬방출인자(CRF) 길항효과를 통해서 내장과민성(visceral hypersensitivity) 및 정신의학적 증상을 호전시키고, 뇌에서 장관으로의 영향(top-down regulation)으로는 우울과 불안을 호전시킴으로 위장관 증상에 영향을 미친 것으로 추정해 볼 수 있다.

• Journal of the Korean Academy of Child and Adolescent Psychiatry
• /
• 제8권2호
• /
• pp.217-231
• /
• 1997

본 연구에서는 ADHD의 원인론에 대한 다양한 신경학적 이론들을 살펴본 후, ADHD 진단에 널리 사용되는 신경심리학적 평가방법들에 대한 국내, 외 연구결과들을 고찰하였다. ADHD 아동들이 여러 주의력 검사상에서 일관성있게 경계력, 지속적 주의력, 주의산만성, 주의력의 분할과 조절에 문제를 보이고 있고, 실행 능력과 작동기억외에 연합기억에서도 어려움을 보이는 것으로 나타났다. 이러한 신경심리학적 검사결과는 ADHD 아동이 전두엽외에 망상활성체계 등 두뇌의 여러 부위를 포함하는 신경망에 장애가 있을 가능성을 시사해주는 것으로 생각된다. 그러나 국내에서 ADHD 아동들에게 널리 사용되고 있는 신경심리검사들은 대부분 외국에서 제작된 것이므로, ADHD 아동들의 수행결과를 보다 정확하게 비교하고 해석하기 위해서는 ADHD와 정상 아동, 그리고 기타 소아정신과장애 아동들을 대상으로 그러한 신경심리검사들에 대한 연령별 규준 확립과 타당도 검증을 위한 한국 표준화연구가 조만간 이루어져야 하겠다.

• Journal of Ginseng Research
• /
• 제42권1호
• /
• pp.98-106
• /
• 2018

Panax ginseng has been used since ancient times based on the traditional Asian medicine theory and clinical experiences, and currently, is one of the most popular herbs in the world. To date, most of the studies concerning P. ginseng have focused on specific mechanisms of action of individual constituents. However, in spite of many studies on the molecular mechanisms of P. ginseng, it still remains unclear how multiple active ingredients of P. ginseng interact with multiple targets simultaneously, giving the multidimensional effects on various conditions and diseases. In order to decipher the systems-level mechanism of multiple ingredients of P. ginseng, a novel approach is needed beyond conventional reductive analysis. We aim to review the systems-level mechanism of P. ginseng by adopting novel analytical framework-network pharmacology. Here, we constructed a compound-target network of P. ginseng using experimentally validated and machine learning-based prediction results. The targets of the network were analyzed in terms of related biological process, pathways, and diseases. The majority of targets were found to be related with primary metabolic process, signal transduction, nitrogen compound metabolic process, blood circulation, immune system process, cell-cell signaling, biosynthetic process, and neurological system process. In pathway enrichment analysis of targets, mainly the terms related with neural activity showed significant enrichment and formed a cluster. Finally, relative degrees analysis for the target-disease association of P. ginseng revealed several categories of related diseases, including respiratory, psychiatric, and cardiovascular diseases.

• 한국발생생물학회지:발생과생식
• /
• 제7권2호
• /
• pp.69-80
• /
• 2003

대량의 발생 유전학적 연구가 가능한 척추동물로서 최근 제브라피쉬가 새로운 동물모델로 급부상하고 있다 다양한 형태의 돌연변이들로부터 새로운 유전자들이 발굴되어지고 있으며, 인간 유전체의 기능 분석 수단으로 활용되어지고 있다. 신경계의 형성과 분화에 이상이 있는 hendless와 mind bomb이라는 두 가지 돌연변이주에서 positional cloning에 의한 원인 유전자의 발굴과 기능 분석의 예로써 현재 제브라피쉬의 연구 현황을 살펴보고자 한다. headless의 원인 유전자로 Tcf-3가 밝혀졌으며, 초기 발생단계에서 Wnt 신호전달이 두뇌의 형태형성과 영역 결정에서 핵심적 역할을 하고 있다는 사실이 밝혀졌다. mind bomb에서의 비정상적인 신경세포의 운명 결정은 lateral inhibition과 Notch 신호전달의 결함에 의한 것이고, 그 원인 유전자는 Notch ligand인 Delta에 결합하는 새로운 ubiquitin E3 ligase로 밝혀졌다. 이러한 돌연변이를 통한 연구는 현재 인간 질환모델의 개발이라는 방향으로 확대되고 있다.

• Molecules and Cells
• /
• 제38권2호
• /
• pp.145-150
• /
• 2015

Continuous intra- and extracellular stresses induce disorder of $Ca^{2+}$ homeostasis and accumulation of unfolded protein in the endoplasmic reticulum (ER), which results in ER stress. Severe long-term ER stress triggers apoptosis signaling pathways, resulting in cell death. Neural epidermal growth factor-like like protein 2 (NELL2) has been reported to be important in protection of cells from cell death-inducing environments. In this study, we investigated the cytoprotective effect of NELL2 in the context of ER stress induced by thapsigargin, a strong ER stress inducer, in Cos7 cells. Overexpression of NELL2 prevented ER stress-mediated apoptosis by decreasing expression of ER stress-induced C/EBP homologous protein (CHOP) and increasing ER chaperones. In this context, expression of anti-apoptotic Bcl-xL was increased by NELL2, whereas NELL2 decreased expression of pro-apoptotic proteins, such as cleaved caspases 3 and 7. This anti-apoptotic effect of NELL2 is likely mediated by extracellular signal-regulated kinase (ERK) signaling, because its inhibitor, U0126, inhibited effects of NELL2 on the expression of anti- and pro-apoptotic proteins and on the protection from ER stress-induced cell death.

• 센서학회지
• /
• 제10권1호
• /
• pp.52-61
• /
• 2001

이 논문에서는 선택적 주의 집중 기능을 갖는 도약 안구 시각 시스템을 제안한다. Saliency map 모델은 주어진 자연 영상에 대하여 선택위치를 순차적으로 출력하여 시선 이동 경로를 발생시킨다. 발생한 선택위치로의 신속한 움직임을 위하여 도약 안구 운동 모델을 개발하였다. 도약 안구 운동 모델은 시각 자극에 의한 반사적 도약 안구 운동 발생 시각 경로를 세 부분으로 구분하고, 시각 경로에 포함되는 뇌 조직들의 기능 및 역할이 반영되도록 각각의 세부 경로를 서로 다른 신경회로망을 이용하여 모델 하였다. 구현한 Saliency map 모델과 도약 안구운동 모델을 기반으로 한 능동 시각 시스템을 CCD 카메라와 BLDC 모터를 이용하여 실제 구성하고, 제안한 능동 시각 시스템이 실제 도약 안구의 움직임을 잘 추종하는지를 실험을 통하여 검증하였다.

• Clinical Psychopharmacology and Neuroscience
• /
• 제16권4호
• /
• pp.415-421
• /
• 2018

Objective: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairment in social skills and communication with repetitive behaviors. Etiology is still unclear although it is thought to develop with interaction of genes and environmental factors. Oxytocin has extensive effects on intrauterine brain development. Vitamin D, affects neural development and differentiation and contributes to the regulation of around 900 genes including oxytocin receptor gene. In the present study, the contribution of D vitamin receptor and oxytocin receptor gene polymorphisms in the development of ASD in Turkish community was investigated. To our knowledge, this is the first study examining these two associated genes together in the literature. Methods: Eighty-five patients diagnosed with ASD according to DSM-5 who were referred to outpatient clinics of Child and Adolescent Psychiatry of Başkent University and Mersin University and 52 healthy, age and gender-matched controls were included in the present study. Vitamin D receptor gene rs731236 (Taq1), rs2228570 (Fok1), rs1544410 (Bsm1), rs7975232 (Apa1) polymorphisms and oxytocin receptor gene rs1042778 and rs2268493 polymorphisms were investigated using real time polymerase chain reaction method. Results: No significant difference between groups in terms of distribution of genotype and alleles in each of polymorphisms for these genes could be found. Conclusion: Knowledge of genes and polymorphisms associated with the development of ASD may be beneficial for early diagnosis and future treatment. Further studies with larger populations are required to demonstrate molecular pathways which may play part in the development of ASD in Turkey.

• The Korean Journal of Physiology and Pharmacology
• /
• 제25권2호
• /
• pp.97-109
• /
• 2021

Neonatal hypoxia/ischemia (H/I), injures white matter, results in neuronal loss, disturbs myelin formation, and neural network development. Neuroinflammation and oxidative stress have been reported in neonatal hypoxic brain injuries. We investigated whether Paeoniflorin treatment reduced H/I-induced inflammation and oxidative stress and improved white matter integrity in a neonatal rodent model. Seven-day old Sprague-Dawley pups were exposed to H/I. Paeoniflorin (6.25, 12.5, or 25 mg/kg body weight) was administered every day via oral gavage from postpartum day 3 (P3) to P14, and an hour before induction of H/I. Pups were sacrificed 24 h (P8) and 72 h (P10) following H/I. Paeoniflorin reduced the apoptosis of neurons and attenuated cerebral infarct volume. Elevated expression of cleaved caspase-3 and Bad were regulated. Paeoniflorin decreased oxidative stress by lowering levels of malondialdehyde and reactive oxygen species generation and while, and it enhanced glutathione content. Microglial activation and the TLR4/NF-κB signaling were significantly down-regulated. The degree of inflammatory mediators (interleukin 1β and tumor necrosis factor-α) were reduced. Paeoniflorin markedly prevented white matter injury via improving expression of myelin binding protein and increasing O1-positive olidgodendrocyte and O4-positive oligodendrocyte counts. The present investigation demonstrates the potent protective efficiency of paeoniflorin supplementation against H/I-induced brain injury by effectually preventing neuronal loss, microglial activation, and white matter injury via reducing oxidative stress and inflammatory pathways.

• Molecules and Cells
• /
• 제45권8호
• /
• pp.537-549
• /
• 2022

Preproenkephalin (PPE) is a precursor molecule for multiple endogenous opioid peptides Leu-enkephalin (ENK) and Met-ENK, which are involved in a wide variety of modulatory functions in the nervous system. Despite the functional importance of ENK in the brain, the effect of brain-derived factor(s) on PPE expression is unknown. We report the dual effect of neural epidermal growth factor (EGF)-like-like 2 (NELL2) on PPE gene expression. In cultured NIH3T3 cells, transfection of NELL2 expression vectors induced an inhibition of PPE transcription intracellularly, in parallel with downregulation of protein kinase C signaling pathways and extracellular signal-regulated kinase. Interestingly, these phenomena were reversed when synthetic NELL2 was administered extracellularly. The in vivo disruption of NELL2 synthesis resulted in an increase in PPE mRNA level in the rat brain, suggesting that the inhibitory action of intracellular NELL2 predominates the activation effect of extracellular NELL2 on PPE gene expression in the brain. Biochemical and molecular studies with mutant NELL2 structures further demonstrated the critical role of EGF-like repeat domains in NELL2 for regulation of PPE transcription. These are the first results to reveal the spatio-specific role of NELL2 in the homeostatic regulation of PPE gene expression.

• 한국컴퓨터정보학회:학술대회논문집
• /
• 한국컴퓨터정보학회 2021년도 제64차 하계학술대회논문집 29권2호
• /
• pp.701-702
• /
• 2021

The purpose of the study was to identify fiber changes induced by electrical stimulation of a certain neural substrate in the rat brain. In the stimulation group, the peripheral nerve was injured and the brain area associated to inhibit sensory information was electrically stimulated. There were sham and sham stimulation groups as controls. Then high-field diffusion tensor imaging (DTI) was acquired. 35 features were taken from the DTI measures from 7 different brain pathways. To compare the efficacy of the classification for 3 animal groups, the linear regression analysis (LDA) and the machine learning technique (MLP) were applied. It was found that the testing accuracy by MLP was about 77%, but that of accuracy by LDA was much higher than MLP. In conclusion, machine learning algorithm could be used to identify and predict the changes of the brain white matter in some situations. The limits of this study will be discussed.