• Biomolecules & Therapeutics
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• 제31권3호
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• pp.264-275
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• 2023

Parkinson's disease (PD) is a common neurodegenerative disorder characterized by tremors, bradykinesia, and rigidity. PD is caused by loss of dopaminergic (DA) neurons in the midbrain substantia nigra (SN) and therefore, replenishment of DA neurons via stem cell-based therapy is a potential treatment option. Astrocytes are the most abundant non-neuronal cells in the central nervous system and are promising candidates for reprogramming into neuronal cells because they share a common origin with neurons. The ability of neural progenitor cells (NPCs) to proliferate and differentiate may overcome the limitations of the reduced viability and function of transplanted cells after cell replacement therapy. Achaete-scute complex homolog-like 1 (Ascl1) is a well-known neuronal-specific factor that induces various cell types such as human and mouse astrocytes and fibroblasts to differentiate into neurons. Nurr1 is involved in the differentiation and maintenance of DA neurons, and decreased Nurr1 expression is known to be a major risk factor for PD. Previous studies have shown that direct conversion of astrocytes into DA neurons and NPCs can be induced by overexpression of Ascl1 and Nurr1 and additional transcription factors genes such as superoxide dismutase 1 and SRY-box 2. Here, we demonstrate that astrocytes isolated from the ventral midbrain, the origin of SN DA neurons, can be effectively converted into DA neurons and NPCs with enhanced viability. In addition, when these NPCs are inducted to differentiate, they exhibit key characteristics of DA neurons. Thus, direct conversion of midbrain astrocytes is a possible cell therapy strategy to treat neurodegenerative diseases.

• BMB Reports
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• 제57권8호
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• pp.363-368
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• 2024

Parkinson's disease (PD), characterized by dopaminergic neuron degeneration in the substantia nigra, is caused by various genetic and environmental factors. Current treatment methods are medication and surgery; however, a primary therapy has not yet been proposed. In this study, we aimed to develop a new treatment for PD that induces direct reprogramming of dopaminergic neurons (iDAN). Achaete-scute family bHLH transcription factor 1 (ASCL1) is a primary factor that initiates and regulates central nervous system development and induces neurogenesis. In addition, it interacts with BRN2 and MYT1L, which are crucial transcription factors for the direct conversion of fibroblasts into neurons. Overexpression of ASCL1 along with the transcription factors NURR1 and LMX1A can directly reprogram iDANs. Using a retrovirus, GFP-tagged ASCL1 was overexpressed in astrocytes. One week of culture in iDAN convertsion medium reprogrammed the astrocytes into iDANs. After 7 days of differentiation, TH+/TUJ1+ cells emerged. After 2 weeks, the number of mature TH+/TUJ1+ dopaminergic neurons increased. Only ventral midbrain (VM) astrocytes exhibited these results, not cortical astrocytes. Thus, VM astrocytes can undergo direct iDAN reprogramming with ASCL1 alone, in the absence of transcription factors that stimulate dopaminergic neurons development.

• 대한수의학회지
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• 제33권3호
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• pp.361-368
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• 1993

The midbrain periaqueductal gray is a midline structure that encircles the mesencephalic aqueduct of midbrain and plays an important role in anaglgesia and modulation of nociceptive input to the central nervous system. It has been demonstrated that the periaqueductal gray contains several neuropeptides including neurotensin, which has been postulated antinociceptive effect to the periaqueductal gray. The present study was performed to provide immunohistochemical localization of neurotensin of midbrain periaqueductal gray in the Korean native goat by using immunohistochemical method. Neurotensin-like immunireactive neurons were localized throughout the midbrain periaqueductal gray, although more immunoreactive neurons were present in the middle and caudal parts of periaquductal gray than the rostral part. Dense neurotensin-like immunoreactive neurons were much more numerous in the ventral lateral division of the mid- and caudal periaqueductal grays. Neurotensin-like immunoreactive neurons were much larger and more prominent near the external margin of the gray than in the juxta-aqueductal region. Neurotensin-like immunoreactive fibers were observed as short processes extending from immunoreactive cells and some small immunoreactive puncta and varicose-like fibers were also seen.

• 대한수의학회지
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• 제37권3호
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• pp.489-497
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• 1997

The distributions characteristics of neurons displaying immunoreactivity to the catecholamine synthetic enzymes, tyrosine hydroxylase(TH), dopamine-${\beta}$-hydroxylase(DBH), and phenylethanolamine-N-methyltransferase(PNMT) were examined in the adjacent sections of the substantia nigra & ventral tegmentum of the Striped Field Mouse(Apodemus agrarius coreae). None of these cell groups displayed either DBH or PNMT immunoreactivity. Many TH-immunoreactive neurons were present in the substantia nigra & ventral tegmentum. The major dopaminergic cell(TH-positive, DBH- & PNMT-negative) group in the midbrain was present in the pars compacta of substantia nigra and adjacent ventral tegmentum. And smaller dopaminergic cell groups Were found in the pars reticulata of the substantia nigra and central liner nucleus.

• The Korean Journal of Physiology and Pharmacology
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• 제2권1호
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• pp.9-19
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• 1998

The present study was primarily carried out to characterize the properties of the spinomesencephalic tract (SMT) neurons that project from the upper cervical spinal segments to the midbrain. It was also investigated whether these neurons received convergent afferent inputs from other sources in addition to cervical inputs. Extracellular single unit recordings were made from neurons antidromically activated by stimulation of midbrain. Recording sites were located in lamina $I{\sim}VIII\;of\;C1{\sim}C3$ segments of spinal cord. Receptive field (RF) and response properties to mechanical stimulation were studied in 71 SMT neurons. Response profiles were classified into six groups: complex (Comp, n=9), wide dynamic range (WDR, n=16), low threshold (LT, n=5), high threshold (HT, n=6), deep/tap (Deep, n=10), and non- responsive (NR, n=25). Distributions of stimulation and recording sites were not significantly different between SMT groups classified upon their locations and/or response profiles. Mean conduction velocity of SMT neurons was $16.7{\pm}1.28\;m/sec$. Conduction velocities of SMTs recorded in superficial dorsal horn (SDH, n=15) were significantly slower than those of SMTs recorded in deep dorsal horn (DDH, n=18), lateral reticulated area (LRA, n=21), and intermediate zone and ventral horn (IZ/VH, n=15). Somatic RFs for SMTs in LRA and IZ/VH were significantly larger than those in SDH and DDH. Five SMT units (4 Comps and 1 HT) had inhibitory somatic RFs. About half (25/46) of SMT units have their RFs over trigeminal dermatome. Excitabilities of 5/12 cells and 9/13 cells were modulated by stimulation of ipsilateral phrenic nerve and vagus nerve, respectively. These results suggest that upper cervical SMT neurons are heterogenous in their function by showing a wide range of variety in location within the spinal gray matter, in response profile, and in convergent afferent input.

• Animal cells and systems
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• 제2권1호
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• pp.71-80
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• 1998

Glutamate dehydrogenase (GDH) is one of the main enzymes involved in the formation and metabolism of the neurotransmitter glutamate. In the present study, we investigated the distribution of the GDH-immunoreactive cells in the rat brain using monoclonal antibodies against bovine brain GDH isoprotein. GDH-immunoreactive cell were distributed in the basal ganglia, thalamus and the nuclei belong to substantia innominata, and its connecting area, subthalamic nucleus, zona incerta, and substantia niqra. We could see GDH-immunoreactive cells in the hippocampus, septal nuclei associated with the limbic system, the anterior thalamic nuclei connecting between the hypothalamus and limbic system, and its associated structures, amygdaloid nuclear complex, the dorsal raphe and median raphe nuclei and the reticular formation of the midbrain. The GDH-immunoreactive cells were shown in the pyramidal neurons of the cerebral cortex, the Purkinie cells of the cerebella cortex, their associated structures, ventral thalamic nuclei and the reticular thalamic nuclei that seem to function as neural conduction in the thalamus.

• Investigative Magnetic Resonance Imaging
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• 제18권2호
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• pp.167-170
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• 2014

내측세로다발은 조화로운 눈운동의 핵심적인 역할을 하는 유수 합성로이며 수도관주위회색질의 배쪽의 중간선 근처에 놓여있다. 내측세로다발의 병변은 신경핵사이 눈근육마비로 불리는 동측의 내전 결손과 반대측 외전 안진을 야기한다. 중뇌와 교뇌에서 인접한 백질과 섞여있는 신경로는 전산화단층촬영술과 자기공명영상과 같은 뇌영상에서 구별하기 어렵다. 지금까지 우리가 알기로는 내측세로다발은 실제 자기공명영상에서 구체적으로 묘사되지 않았다. 우리는 염증성 탈수초성 질환에서 자기공명영상에 내측세로다발의 전체 연결 과정을 보이는 증례를 보고한다.

• Annals of Clinical Neurophysiology
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• 제4권1호
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• pp.56-59
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• 2002

A 28-year-old man presented with headache, fever, and myalgia. Subsequently, rapidly progressive quadriplegia with areflexia developed. CSF examination revealed moderate pleocytosis and protein elevation. MRI of brain and spinal cord showed hyperintense lesions on T2-weighted image at midbrain and ventral horns along the whole spinal cord. Serial serologic examinations of CSF for Epstein-Barr virus and cytomegalovirus were negative. Culture and neutralization tests of stool and CSF for enterovirus were negative. Although the etiologic pathogen was not identified, we diagnosed him as poliomyelitis-like syndrome by clinical features and findings of MRI.

• Annals of Clinical Neurophysiology
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• 제3권2호
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• pp.168-171
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• 2001

It has been said that variable anatomical structures and neural circuits are related to the generation of tremor. There are cerebral cortex, thalamus, basal ganglia, inferior olivary nucleus, midbrain tegmentum, stretch reflex, and musculoskeletal structures. The stretch reflex is related with the physiologic tremor and various peripherally originated tremors. We experienced a case with the post-stroke resting tremor which was induced and aggravated by mechanical stretching stimulation. In the present case, stretch reflex has a major role in the generation and exacerbation of tremor. It is presumed that the development of tremor is attributed to the increased rhythmicity of ventral intermedius nucleus of thalamus. The enhancement of thalamic rhythmicity may be due to the increasement of long latency reflex by post-stroke rigidity. This case suggests that stretch reflex may have a major role in the pathophysiologic mechanisms of a certain centrally originated tremor.

• 통합자연과학논문집
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• 제15권2호
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• pp.63-72
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• 2022

To elucidate the neurochemical characteristics of the midbrain periaqueductal gray (PAG), the distribution patterns of several neuroanatomical markers within the PAG were compared. Immunohistochemical staining for the intracellular calcium binding proteins including calbindin, calretinin, and parvalbumin and histochemical staining for cytochrome oxidase, acetylcholinesterase, and NADPH-diaphorase were performed in. Each chemical substance were localized in the specific subregions within PAG. Calbindin- immunoreactivity were selectively distributed in the dorsolateral PAG, the ventral half of lateral PAG, the ventralateral PAG, and supraoculomotor cap (Su3C) nucleus. Distribution of calretinin-immunoreactivity were generally similar with that of clabindin, but showed relatively low subregional selectivity. Parvalbumin-immunoreactivity was very poor within the PAG. High reactivity of cytochrome oxidase were found in the dorsomedial PAG and the lateral half of lateral PAG, in which calbindin- and calretinin-immunoreactive perikarya were scarcely observed. Acetylcholinesterase distribution was similar with that of cytochrome oxidase, and the difference was in the additional marking of of Su3C with acetylcholinesterase. Results of the present study provides data for the further subdivisions of the territory of the PAG compared to the presently accepted subregions within the PAG.