• Biomolecules & Therapeutics
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• 제32권4호
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• pp.403-423
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• 2024

The human gastrointestinal (GI) tract houses a diverse microbial community, known as the gut microbiome comprising bacteria, viruses, fungi, and protozoa. The gut microbiome plays a crucial role in maintaining the body's equilibrium and has recently been discovered to influence the functioning of the central nervous system (CNS). The communication between the nervous system and the GI tract occurs through a two-way network called the gut-brain axis. The nervous system and the GI tract can modulate each other through activated neuronal cells, the immune system, and metabolites produced by the gut microbiome. Extensive research both in preclinical and clinical realms, has highlighted the complex relationship between the gut and diseases associated with the CNS, such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. This review aims to delineate receptor and target enzymes linked with gut microbiota metabolites and explore their specific roles within the brain, particularly their impact on CNS-related diseases.

• 인터넷정보학회논문지
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• 제15권4호
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• pp.9-20
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• 2014

대상의 동작을 잘 예측하는 것은 사회적 상호작용과 의사결정 컨텍스트 이해의 핵심이다. 본 연구는 동작 인식 과정에서 인간 뇌 시각인지 과정을 모방한 방법으로 관절 동작의 동작 순서 패턴을 학습하는 컴퓨팅 모델을 제안하였다. 제안 방법의 핵심은 뇌에서 동작 인지 자극을 처리하는 신경생리학적 IT, MT, STS의 피질 기능과 특정 시각 신경 회로 네트워크 기능을 모방하여 비지도 방법으로 동작 순서를 학습한 후 동작을 예측, 인식하는 것이다. 실험을 통해 제안 모델이 어떻게 연속적으로 입력되는 비디오에서 의미있는 동작 스냅샷 뿐 아니라 중요한 동작 패턴을 자동으로 선택하는 지를 제시하였다. 이 핵심 움직임은 학습 네트워크가 정적 시점에서 정지 영상에 함축된 동작을 인식하는지를 증명하는데 이용하는 관절 자세이다. 또한 STS 피질 영역에서 어떻게 정지와 움직임 입력을 통합하는지를 모방하여 학습하고, 학습한 피드백 연결이 차후 동작의 입력 순서를 어떻게 예측하는지를 제시하였다. 네트워크 시뮬레이션을 통해 동작 인식에 대한 제안 모델의 우수성을 입증하였다.

• 한국정보전자통신기술학회논문지
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• 제16권1호
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• pp.1-7
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• 2023

시각 피질로부터 영감을 심층 신경망의 일종인 컨벌루션 신경망은 영상 관련 분야에서 이미 인간의 시각처리 능력을 넘어서 다양한 분야에 응용되고 있지만 적대적 공격의 출현으로 모델의 성능이 저하되는 심각한 위험에 노출되어 있다. 또한 적대적 공격에 대응하기 위한 방어 기술은 해당 공격에 효과를 보이지만 다른 종류의 공격에는 취약하다. 적대적 공격에 대응하기 위해서는 적대적 공격이 컨벌루션 신경망 내부에서 어떤 과정을 통하여 성능이 저하되는 지에 대한 분석이 필요하다. 본 연구에서는 신경생리학 분야에서 뉴런의 활동을 측정하기 위한 척도인 개체군 희소성 인덱스를 이용하여 AlexNet과 VGG11 모델의 적대적 공격에 대한 분석을 수행하였다. 수행된 연구를 통하여 적대적 예제에 대한 개체군 희소성 인덱스가 AlexNet에서는 전 연결 층에서 개체군 희소성이 증가하는 현상을 발견할 수 있었으며 이와 같은 동작은 일반적인 신경망의 동작에 반하는 결과로서 적대적 예제가 신경망의 동작에 영향을 미치고 있다는 강력한 증거이며 또한 동일한 실험을 실시한 VGG11에서는 전체 레이어에서 개체군 희소성 인덱스가 전반적으로 감소하여 개체 인식의 성능이 감소되는 활동을 관찰 할 수 있었다. 이와 같은 결과는 신경생리학적 관점에서 뉴런의 활동을 관찰하는 방식을 인공지능 분야에서도 활용하고 분석할 수 있는 방법을 제시하였다.

• 한국가축번식학회지
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• 제25권4호
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• pp.389-397
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• 2001

CART는 leptin에 의해 조절되는 포식인자이며 섭식과 운동 습성에 관계된 것으로 알려져 있다. 사람의 CART Leu34Phe 돌연변이는 비만의 표현형을 나타내었지만, 생쥐의 CART 돌연변이는 일반사료의 섭취 후 급격한 체중증가를 나타내지는 않았다 생체 내 신경세포에서 CART의 역할을 확인하기 위한 새로운 형질전환 모델을 확립하고자 분화하는 신경세포의 유전자 발현을 조절하는 NF-L promoter와 CART의 재조합 발현 벡터를 구축하였다. 형질전환 생쥐는 유전자 미세 주입법에 의하여 생산되었으며, PCR과 Southern blot의 방법으로 확인하였다. 이러한 형질전환 생쥐에서 CART의 과 발현을 수정 후 13.5일째 초기 배아와 생후 6주째 형질전환 생쥐의 뇌와 척수에서 확인하였다. 본 연구의 결과는 섭식 관련 유전자들이 상호 연관된 섭식행동에서 CART의 역할을 연구하는데 모델 동물로써 이용할 수 있을 것으로 사료된다.

• Molecules and Cells
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• 제40권7호
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• pp.450-456
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• 2017

Mammalian physiology and behavior are regulated by an internal time-keeping system, referred to as circadian rhythm. The circadian timing system has a hierarchical organization composed of the master clock in the suprachiasmatic nucleus (SCN) and local clocks in extra-SCN brain regions and peripheral organs. The circadian clock molecular mechanism involves a network of transcription-translation feedback loops. In addition to the clinical association between circadian rhythm disruption and mood disorders, recent studies have suggested a molecular link between mood regulation and circadian rhythm. Specifically, genetic deletion of the circadian nuclear receptor Rev-$erb{\alpha}$ induces mania-like behavior caused by increased midbrain dopaminergic (DAergic) tone at dusk. The association between circadian rhythm and emotion-related behaviors can be applied to pathological conditions, including neurodegenerative diseases. In Parkinson's disease (PD), DAergic neurons in the substantia nigra pars compacta progressively degenerate leading to motor dysfunction. Patients with PD also exhibit non-motor symptoms, including sleep disorder and neuropsychiatric disorders. Thus, it is important to understand the mechanisms that link the molecular circadian clock and brain machinery in the regulation of emotional behaviors and related midbrain DAergic neuronal circuits in healthy and pathological states. This review summarizes the current literature regarding the association between circadian rhythm and mood regulation from a chronobiological perspective, and may provide insight into therapeutic approaches to target psychiatric symptoms in neurodegenerative diseases involving circadian rhythm dysfunction.

• The Korean Journal of Pain
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• 제32권4호
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• pp.271-279
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• 2019

Background: We utilized diffusion tensor imaging (DTI) to evaluate the cerebral white matter changes that are associated with phantom limb pain in patients with unilateral arm amputation. It was anticipated that this would complement previous research in which we had shown that changes in cerebral blood volume were associated with the cerebral pain network. Methods: Ten patients with phantom limb pain due to unilateral arm amputation and sixteen healthy age-matched controls were enrolled. The intensity of phantom limb pain was measured by the visual analogue scale (VAS) and depressive mood was assessed by the Hamilton depression rating scale. Diffusion tensor-derived parameters, including fractional anisotropy, mean diffusivity, axial diffusivity (AD), and radial diffusivity (RD), were computed from the DTI. Results: Compared with controls, the cases had alterations in the cerebral white matter as a consequence of phantom limb pain, manifesting a higher AD of white matter in both hemispheres symmetrically after adjusting for individual depressive moods. In addition, there were associations between the RD of white matter and VAS scores primarily in the hemispheres related to the missing hand and in the corpus callosum. Conclusions: The phantom limb pain after unilateral arm amputation induced plasticity in the white matter. We conclude that loss of white matter integrity, particularly in the hemisphere connected with the missing hand, is significantly correlated with phantom limb pain.

• BMB Reports
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• 제54권11호
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• pp.557-562
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• 2021

Microglial activation is closely associated with neuroinflammatory pathologies. The nucleotide-binding and oligomerization domain-like receptor containing a pyrin domain 3 (NLRP3) inflammasomes are highly organized intracellular sensors of neuronal alarm signaling. NLRP3 inflammasomes activate nuclear factor kappa-B (NF-κB) and reactive oxygen species (ROS), which induce inflammatory responses. Moreover, NLRP3 dysfunction is a common feature of chronic inflammatory diseases. The present study investigated the effect of a novel thiazol derivative, N-cyclooctyl-5-methylthiazol-2-amine hydrobromide (KHG26700), on inflammatory responses in lipopolysaccharide (LPS)-treated BV-2 microglial cells. KHG26700 significantly attenuated the expression of several pro-inflammatory cytokines, including tumor necrosis factor-α, interleukin-1β, and interleukin-6, in these cells, as well as the LPS-induced increases in NLRP3, NF-κB, and phospho-IkBα levels. KHG26700 also suppressed the LPS-induced increases in protein levels of autophagy protein 5 (ATG5), microtubule-associated protein 1 light chain 3 (LC3), and beclin-1, as well as downregulating the LPS-enhanced levels of ROS, lipid peroxidation, and nitric oxide. These results suggest that the anti-inflammatory effects of KHG26700 may be due, at least in part, to the regulation of the NLRP3-mediated signaling pathway during microglial activation.

• 대한약침학회지
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• 제27권2호
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• pp.162-171
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• 2024

Objectives: Electroacupuncture (EA) has been demonstrated to aid stroke recovery. However, few investigations have focused on identifying the potent molecular targets of EA by comparing EA stimulation between naïve and disease models. Therefore, this study was undertaken to identify the potent molecular therapeutic mechanisms underlying EA stimulation in ischemic stroke through a comparison of mRNA sequencing data obtained from EA-treated naïve control and ischemic stroke mouse models. Methods: Using both naïve control and middle cerebral artery occlusion (MCAO) mouse models, EA stimulation was administered at two acupoints, Baihui (GV20) and Dazhui (GV14), at a frequency of 2 Hz. Comprehensive assessments were conducted, including behavioral evaluations, RNA sequencing to identify differentially expressed genes (DEGs), functional enrichment analysis, protein-protein interaction (PPI) network analysis, and quantitative real-time PCR. Results: EA stimulation ameliorated the ischemic insult-induced motor dysfunction in mice with ischemic stroke. Comparative analysis between control vs. MCAO, control vs. control + EA, and MCAO vs. MCAO + EA revealed 4,407, 101, and 82 DEGs, respectively. Of these, 30, 7, and 1 were common across the respective groups. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses revealed upregulated DEGs associated with the regulation of inflammatory immune response in the MCAO vs. MCAO + EA comparison. Conversely, downregulated DEGs in the control vs. control + EA comparison were linked to neuronal development. PPI analysis revealed major clustering related to the regulation of cytokines, such as Cxcl9, Pcp2, Ccl11, and Cxcl13, in the common DEGs of MCAO vs. MCAO + EA, with Esp8l1 identified as the only common downregulated DEG in both EA-treated naïve and ischemic models. Conclusion: These findings underscore the diverse potent mechanisms of EA stimulation between naïve and ischemic stroke mice, albeit with few overlaps. However, the potent mechanisms underlying EA treatment in ischemic stroke models were associated with the regulation of inflammatory processes involving cytokines.

• IMMUNE NETWORK
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• 제22권2호
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• pp.20.1-20.9
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• 2022

Despite the high prevalence of chronic dermatitis and the accompanied intractable itch, therapeutics that specifically target itching have low efficacy. Increasing evidence suggests that TLRs contribute to immune activation and neural sensitization; however, their roles in chronic itch remain elusive. Here, we show that the RBL-2H3 mast cell line expresses TLR4 and that treatment with a TLR4 antagonist opposes the LPS dependent increase in mRNA levels of Th2 and innate cytokines. The pathological role of TLR4 activation in itching was studied in neonate rats that developed chronic itch due to neuronal damage after receiving subcutaneous capsaicin injections. Treatment with a TLR4 antagonist protected these rats with chronic itch against scratching behavior and chronic dermatitis. TLR4 antagonist treatment also restored the density of cutaneous nerve fibers and inhibited the histopathological changes that are associated with mast cell activation after capsaicin injection. Additionally, the expression of IL-1β, IL-4, IL-5, IL-10, and IL-13 mRNA in the lesional skin decreased after TLR4 antagonist treatment. Based on these data, we propose that inhibiting TLR4 alleviated itch in a rat model of chronic relapsing itch, and the reduction in the itch was associated with TLR4 signaling in mast cells and nerve fibers.

• BMB Reports
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• 제39권4호
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• pp.339-345
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• 2006

The blood-neural barrier (BNB), including blood-brain barrier (BBB) and blood-retinal barrier (BRB), is an endothelial barrier constructed by an extensive network of endothelial cells, astrocytes and neurons to form functional 'neurovascular units', which has an important role in maintaining a precisely regulated microenvironment for reliable neuronal activity. Although failure of the BNB may be a precipitating event or a consequence, the breakdown of BNB is closely related with the development and progression of CNS diseases. Therefore, BNB is most essential in the regulation of microenvironment of the CNS. The BNB is a selective diffusion barrier characterized by tight junctions between endothelial cells, lack of fenestrations, and specific BNB transporters. The BNB have been shown to be astrocyte dependent, for it is formed by the CNS capillary endothelial cells, surrounded by astrocytic end-foot processes. Given the anatomical associations with endothelial cells, it could be supposed that astrocytes play a role in the development, maintenance, and breakdown of the BNB. Therefore, astrocytes-endothelial cells interaction influences the BNB in both physiological and pathological conditions. If we better understand mutual interactions between astrocytes and endothelial cells, in the near future, we could provide a critical solution to the BNB problems and create new opportunities for future success of treating CNS diseases. Here, we focused astrocyte-endothelial cell interaction in the formation and function of the BNB.