• 전자통신동향분석
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• 제33권6호
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• pp.58-68
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• 2018

A neuromorphic hardware that mimics biological perceptions and has a path toward human-level artificial intelligence (AI) was developed. In contrast with software-based AI using a conventional Von Neumann computer architecture, neuromorphic hardware-based AI has a power-efficient operation with simultaneous memorization and calculation, which is the operation method of the human brain. For an ideal neuromorphic device similar to the human brain, many technical huddles should be overcome; for example, new materials and structures for the synapses and neurons, an ultra-high density integration process, and neuromorphic modeling should be developed, and a better biological understanding of learning, memory, and cognition of the brain should be achieved. In this paper, studies attempting to overcome the limitations of next-generation neuromorphic hardware technologies are reviewed.

• Biomolecules & Therapeutics
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• 제29권1호
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• pp.83-89
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• 2021

Multiple system atrophy (MSA) is a neurodegenerative disease characterized by presence of α-synuclein-positive inclusions in the cytoplasm of oligodendrocytes. These glial cytoplasmic inclusions (GCIs) are considered an integral part of the pathogenesis of MSA, leading to demyelination and neuronal demise. What is most puzzling in the research fields of GCIs is the origin of α-synuclein aggregates in GCIs, since adult oligodendrocytes do not express high levels of α-synuclein. The most recent leading hypothesis is that GCIs form via transfer and accumulation of α-synuclein from neurons to oligodendrocytes. However, studies regarding this subject are limited due to the absence of proper human cell models, to demonstrate the entry and accumulation of neuronal α-synuclein in human oligodendrocytes. Here, we generated mature human oligodendrocytes that can take up neuronderived α-synuclein and form GCI-like inclusions. Mature human oligodendrocytes are derived from neural stem cells via "oligosphere" formation and then into oligodendrocytes, treating the cells with the proper differentiation factors at each step. In the final cell preparations, oligodendrocytes consist of the majority population, while some astrocytes and unidentified stem cell-like cells were present as well. When these cells were exposed to α-synuclein proteins secreted from neuron-like human neuroblastoma cells, oligodendrocytes developed perinuclear inclusion bodies with α-synuclein immunoreactivity, resembling GCIs, while the stem cell-like cells showed α-synuclein-positive, scattered puncta in the cytoplasm. In conclusion, we have established a human oligodendrocyte model for the study of GCI formation, and the characterization and use of this model might pave the way for understanding the pathogenesis of MSA.

• 한국발생생물학회지:발생과생식
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• 제11권3호
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• pp.235-243
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• 2007

인간 제대혈 세포는 조혈모세포, 중간엽 줄기세포와내피전구세포를 풍부하게 포함하고 있다. 인간 제대혈 속의 중간엽 줄기세포는 조혈모세포와는 달리 다능성 줄기세포이며 신경세포로 분화할 수 있는 잠재성을 가지고 있다. 본 연구에서는 세포배양을 통해 제대혈의 중간엽 줄기세포를 신경세포와 콜린성 신경세포로 분화를 유도하였다. 중간엽 줄기세포를 신경세포로 분화시키기 위해 배양액에 dimethyl sulphoxide(DMSO)와 butylated hydroxyanisole(BHA)를 첨가하여 유도하였으며 basic fibroblast growth factor(bFGF), retinoic acid(RA), sonic hedgehog(Shh)를 처리하여 콜린성 신경세포로 분화시켰다. DMSO와 BHA에 처리된 중간엽 줄기세포가 빠르게 신경세포 모양으로 분화하는 것을 관찰하였으며, 이것은 면역조직학적 염색에서 신경세포 특이 표지인 $\beta$-tubulin III, 별아교세포에 대한 특이 표지인 GFAP, 희돌기아교세포에 대한 특이 표지인 Gal-C에 대해 양성반응을 나타내었고, 그 비율은 각각 $32.3{\pm}2.9%$, $11.0{\pm}0.9%,\;9.4{\pm}1.0%$였다. RT-PCR 분석에서 배양 단계에 따라 신경세포에 특이적인 표지 인자가 발현됨을 통해, 중간엽 줄기세포가 신경세포로 분화됨을 확인하였다. 또한, 중간엽 줄기세포에 bFGF, RA, Shh를 처리하여 콜린성 신경세포로 분화시켰을 때, 전체 중간엽 세포 중 $31.3{\pm}3.2%$가 신경세포 특이 표지인 $\beta$-tubulin III에 양성반응을 보였으며 이들 세포 중 $70.0{\pm}7.8%$가 콜린성 신경 특이 표지인 ChAT에 양성반응을 보였고, 이것은 Woodbury 방법에 의한 신경분화의 경우보다 3배 가량 높은 비율로 콜린성 신경의 분화를 유도한 것이다. 이러한 실험 결과들은 인간 제대혈의 중간엽 줄기세포가 콜린성 신경세포로 분화가 가능하고 이러한 잠재성을 가진 제대혈 중간엽 줄기세포는 퇴행성 신경질환에 대한 세포 치료제로서 가능성을 제시한다.

• 인지과학
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• 제23권4호
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• pp.517-551
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• 2012

우리는 모방하는 동물이다. '참된 모방(true imitation)'은 한 행위가 행해진 것을 보는 것으로부터 그 행위를 하는 법을 새롭게 배우는 것이라고 할 수 있다. 우리는 타 개체의 기술과 지식을 모방함으로써 다른 동물의 세계에서 찾아보기 힘든 문화와 문명을 이룩할 수 있었다. 이런 의미에서 모방 능력이 어떻게 진화하고 발달하는지를 묻는 것은 중요하다. 또한 인간이 아닌 다른 동물들이 참된 모방을 할 수 있는지, 그리고 모방 학습 측면에서 인간과 동물이 구체적으로 어떻게 다른지를 알아보는 작업도 매우 흥미로운 과제이다. 이 논문에서 나는 우선, 인간과 다른 동물들의 모방 능력에 대한 경험적 연구들을 검토해볼 것이다. 이런 비교 연구를 통해 동물과 인간의 모방 능력의 차이에 주목할 것이며, 그들에게서 보이는 복제 충실도의 차이가 왜 발생하는지에 대해 논의할 것이다. 그런 다음에 모방의 신경생물학적 메커니즘에 대한 최신 연구들을 검토할 것이다. 하전두회(inferior Frontal Gyrus, IFG)와 하두정엽(inferior Parietal Lobule, IPL)으로 구성된 인간의 거울 뉴런계(mirror neuron system)가 이 대목에서 가장 중요하게 등장한다. 거울 뉴런계는 타 개체의 행동을 이해하고 공감하고 따라하는 데에 필수적인 신경세포 다발이다. 나는 거울 뉴런계의 기능과 진화에 대한 최신 연구들을 소개할 것이다. 인간의 모방을 가능하게 하는 신경 메커니즘에 대한 연구는 처음에 거울 뉴런계와 후부상측두이랑(posterior Superior Temporal Sulcus, pSTS)로 구성된 '핵심 모방 회로'에 집중되어 있었다. 하지만 더 최신의 연구들은 핵심 모방 회로 밖에서도 모방의 신경 메커니즘이 작동한다는 사실을 말해준다. 마지막으로 나는 이러한 모방의 심리학과 생물학이 문화 진화에 어떤 함의를 지니는지를 탐구한다. 구체적으로 나는 밈과 거울뉴런계의 관계를 탐구한 최신 연구를 통해 문화 진화에 대한 밈학적 접근을 시도할 것이다.

• Clinical and Experimental Reproductive Medicine
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• 제29권2호
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• pp.117-127
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• 2002

Objective: This study was to investigate the generation of the functional neuron derived from human embryonic stem (hES, MB03) cells on in vitro neural cell differentiation system. Methods: For neural progenitor cell formation derived from hES cells, we produced embryoid bodies (EB: for 5 days, without mitogen) from hES cells and then neurospheres (for $7{\sim}10$ days, 20 ng/ml of bFGF added N2 medium) from EB. And then finally for the differentiation into mature neuron, neural progenitor cells were cultured in i) N2 medium only (without bFGF), ii) N2 supplemented with 20 ng/ml platelet derived growth factor-bb (PDGF-bb) or iii) N2 supplemented with 5 ng/ml brain derived neurotrophic factor (BDNF) for 2 weeks. Identification of neural cell differentiation was carried out by immunocytochemistry using $\beta_{III}$-tubulin (1:250), MAP-2 (1:100) and GFAP (1:500). Also, generation of functional neuron was identified using anti-glutamate (Sigma, 1:1000), anti-GABA (Sigma, 1:1000), anti-serotonin (Sigma, 1:1000) and anti-tyrosine hydroxylase (Sigma, 1:1000). Results: In vitro neural cell differentiation, neurotrophic factors (PDGF and BDNF) treated cell groups were high expressed MAP-2 and GFAP than non-treated cell group. The highest expression pattern of MAP-2 and $\beta_{III}$-tubulin was indicated in BDNF treated group. Also, in the presence of PDGF-bb or BDNF, most of the neural cells derived from hES cells were differentiated into glutamate and GABA neuron in vitro. Furthermore, we confirmed that there were a few serotonin and tyrosine hydroxylase positive neuron in the same culture environment. Conclusion: This results suggested that the generation of functional neuron derived from hES cells was increased by addition of neurotrophic factors such as PDGF-bb or BDNF in b-FGF induced neural cell differentiation system and especially glutamate and GABA neurons were mainly produced in the system.

• 한국융합학회논문지
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• 제8권10호
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• pp.167-172
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• 2017

본 연구는 그동안 탁월한 치유의 기능이 내재되어 있다고 알려진 시조의 감정 코드들을 분석하여 인문학적 치유의 콘텐츠를 활성화시키고자 하는 데에 목적이 있다. 치유작용의 일환으로써의 시조는 여러 작품들을 감상하는 과정에서 형성되는 감정의 융합을 통해 감정의 총체라 할 수 있는 치유의 감정 코드들을 형성한다. 이러한 과정은 인체생리학적으로 인체 내에서의 문학치료의 진행을 가능하게 한다. 머신러닝이 인지기능에 의해 스스로 학습하는 것처럼 상시적으로 부호화와 재부호화에 대한 코딩 과정이 인체 시스템의 수많은 뉴런들의 집합체들에서 작동된다. 그 과정에서 감정 코드들의 집합적인 부호화에 의해 인체 내에서 아미노산이 합성되는 것으로 예측된다. 이러한 아미노산들이 인체의 신호 체계를 조절하는 것이다. 향후 이러한 인문학과 인체생리학의 접점에서의 치료의 연구가 진행된다면 보다 질 높은 인문학적 치유의 프로그램이 활성화될 것으로 기대된다.

• International Journal of Stem Cells
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• 제17권1호
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• pp.59-69
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• 2024

Human pluripotent stem cells (hPSCs) such as human embryonic stem cells (hESCs), induced pluripotent stem cells, and somatic cell nuclear transfer (SCNT)-hESCs can permanently self-renew while maintaining their capacity to differentiate into any type of somatic cells, thereby serving as an important cell source for cell therapy. However, there are persistent challenges in the application of hPSCs in clinical trials, where one of the most significant is graft rejection by the patient immune system in response to human leukocyte antigen (HLA) mismatch when transplants are obtained from an allogeneic (non-self) cell source. Homozygous SCNT-hESCs (homo-SCNT-hESCs) were used to simplify the clinical application and to reduce HLA mismatch. Here, we present a xeno-free protocol that confirms the efficient generation of neural precursor cells in hPSCs and also the differentiation of dopaminergic neurons. Additionally, there was no difference when comparing the HLA expression patterns of hESC, homo-SCNT-hESCs and hetero-SCNT-hESCs. We propose that there are no differences in the differentiation capacity and HLA expression among hPSCs that can be cultured in vitro. Thus, it is expected that homo-SCNT-hESCs will possess a wider range of applications when transplanted with neural precursor cells in the context of clinical trials.

• 대한전기학회:학술대회논문집
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• 대한전기학회 2015년도 제46회 하계학술대회
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• pp.1243-1244
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• 2015

Finding solutions for the disabled is a major challenge for our society. In the case of a disability due to a malfunction of the nervous system, the origin may be accidental, genetic, or induced by environmental factors. This type of loss can cause loss or movement disorders (paraplegia, hemiplegia, quadriplegia, epilepsy, Parkinson's disease, multiple sclerosis, etc.) or malfunction of certain sensory functions (blindness, deafness, chronic pain, etc.). Many alternatives, more technology, have been imported to create interfaces between the human body and an artificial prosthesis in order to restore some functions of the human body. A wireless system, battery neurons probe was developed for one hand reading neural signals in the brain, and on the other hand also able to excite the neuron in the brain using a surface acoustic wave one ports (SAW) delay line reflection.

• Molecules and Cells
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• 제42권11호
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• pp.739-746
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• 2019

Significant knowledge about the pathophysiology of Alzheimer's disease (AD) has been gained in the last century; however, the understanding of its causes of onset remains limited. Late-onset AD is observed in about 95% of patients, and APOE4-encoding apolipoprotein E4 (ApoE4) is strongly associated with these cases. As an apolipoprotein, the function of ApoE in brain cholesterol transport has been extensively studied and widely appreciated. Development of new technologies such as human-induced pluripotent stem cells (hiPSCs) and CRISPR-Cas9 genome editing tools have enabled us to develop human brain model systems in vitro and readily manipulate genomic information. In the context of these advances, recent studies provide strong evidence that abnormal cholesterol metabolism by ApoE4 could be linked to AD-associated pathology. In this review, we discuss novel discoveries in brain cholesterol dysregulation by ApoE4. We further elaborate cell type-specific roles in cholesterol regulation of four major brain cell types, neurons, astrocytes, microglia, and oligodendrocytes, and how its dysregulation can be linked to AD pathology.

• Biomolecules & Therapeutics
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• 제30권1호
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• pp.38-47
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• 2022

The present study focused on lithocholic acid (LCA), a secondary bile acid that contributes to cholestatic pruritus. Although recent studies have found that LCA acts on MAS-related G protein-coupled receptor family member X4 (MRGPRX4) in humans, it is unclear which subtypes of MRGPRs are activated by LCA in mice since there is no precise ortholog of human MRGPRX4 in the mouse genome. Using calcium imaging, we found that LCA could activate mouse Mrgpra1 when transiently expressed in HEK293T cells. Moreover, LCA similarly activates mouse Mrgprb2. Importantly, LCA-induced responses showed dose-dependent effects through Mrgpra1 and Mrgprb2. Moreover, treatment with QWF (an antagonist of Mrgpra1 and Mrgprb2), YM254890 (Gα_q inhibitor), and U73122 (an inhibitor of phospholipase C) significantly suppressed the LCA-induced responses, implying that the LCA-induced responses are indeed mediated by Mrgpra1 and Mrgprb2. Furthermore, LCA activated primary cultures of mouse sensory neurons and peritoneal mast cells, suggesting that Mrgpra1 and Mrgprb2 contribute to LCA-induced pruritus. However, acute injection of LCA did not induce noticeable differences in scratching behavior, implying that the pruritogenic role of LCA may be marginal in non-cholestatic conditions. In summary, the present study identified for the first time that LCA can activate Mrgpra1 and Mrgprb2. The current findings provide further insight into the similarities and differences between human and mouse MRGPR families, paving a way to understand the complex roles of these pruriceptors.