• 대한의생명과학회지
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• 제15권3호
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• pp.249-255
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• 2009

All living things have been developed efficient strategies to cope with external and internal environmental changes via a process termed 'homeostasis'. However, chronic prenatal maternal stress may significantly contributes to pregnancy complications by disturbing hypothalamic-pituitary-adrenal (HPA) axis and the automatic nervous system (ANS), and results in unfavorable development of the fetus. Dysregulation of these two major stress response systems lead to the increased secretion of the glucocorticoids (GCs) which are known to be essential for normal development and the maturation of the central nervous system. As Hox genes are master key regulators of the embryonic morphogenesis and cell differentiation, we aimed to determine the effects of dexamethasone, a potent synthetic glucocorticoid, on gene expression in mesenchymal stem cell C3H10T1/2. Analysis of 39 Hox genes based on reverse transcription PCR (RT-PCR) method revealed that the expression patterns of Hox genes were overall upregulated by long dexametasone treatment. These results indicate that maternal stress may have a deleterious effect on early developing embryo through the stress hormone, glucocorticoid.

• 대한핵의학회지
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• 제34권4호
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• pp.360-365
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• 2000

We experienced a case of cerebral hypoperfusion due to cyclosporine neurotoxocity confirmed only by Tc-99m ECD brain SPECT. A 53-year-old female had received allogenic peripheral blood stem cell transplantation due to refractory plasmacytoid lymphoma. Cyclosporine and steroid had been administrated to prevent graft versus host disease. Twenty days after transplantation, she became delirious and suffered from generalized tonic-clonic seizure. Immediately, brain MRI and MR angiography were performed and these studies did not show any abnormal findings. However, Tc-99m ECD brain SPECT showed diffuse hypoperfusion in the left cerebral hemisphere and blood cyclosporine level was 962.6 ng/ml. Cyclosporine administration was stopped and discontinuation of cyclosporine resulted in disappearance of all neurological symptoms. The same neurological symptoms recurred with cyclosporine re-administration for management of exacerbated graft versus host disease. In this case, Tc-99m ECD brain SPECT proved very helpful in the diagnosis of cycloporine neurotoxicity.

• Journal of Korean Neurosurgical Society
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• 제58권3호
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• pp.167-174
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• 2015

Objective : This study investigates the role of a burr hole and calvarial bone marrow-derived stem cells (BMSCs) in a transient ischemic brain injury model in the rat and postulates a possible mechanism for the efficacy of multiple cranial burr hole (MCBH) surgery in moyamoya disease (MMD). Methods : Twenty Sprague-Dawley rats (250 g, male) were divided into four groups : normal control group (n=5), burr hole group (n=5), ischemia group (n=5), and ischemia+burr hole group (n=5). Focal ischemia was induced by the transient middle cerebral artery occlusion (MCAO). At one week after the ischemic injury, a 2 mm-sized cranial burr hole with small cortical incision was made on the ipsilateral (left) parietal area. Bromodeoxyuridine (BrdU, 50 mg/kg) was injected intraperitoneally, 2 times a day for 6 days after the burr hole trephination. At one week after the burr hole trephination, brains were harvested. Immunohistochemical stainings for BrdU, CD34, VEGF, and Doublecortin and Nestin were done. Results : In the ischemia+burr hole group, BrdU (+), CD34 (+), and Doublecortin (+) cells were found in the cortical incision site below the burr hole. A number of cells with Nestin (+) or VEGF (+) were found in the cerebral parenchyma around the cortical incision site. In the other groups, BrdU (+), CD34 (+), Doublecortin (+), and Nestin (+) cells were not detected in the corresponding area. These findings suggest that BrdU (+) and CD34 (+) cells are bone marrow-derived stem cells, which may be derived from the calvarial bone marrow through the burr hole. The existence of CD34 (+) and VEGF (+) cells indicates increased angiogenesis, while the existence of Doublecortin (+), Nestin (+) cells indicates increased neurogenesis. Conclusion : Based on these findings, the BMSCs through burr holes seem to play an important role for the therapeutic effect of the MCBH surgery in MMD.

• Molecules and Cells
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• 제26권5호
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• pp.454-458
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• 2008

Sex steroid hormone receptors play a central role in modulating telomerase activity, especially in cancer cells. However, information on the regulation of steroid hormone receptors and their distinct functions on telomerase activity within the mesenchymal stem cell are largely unavailable due to low telomerase activity in the cell. In this study, the effects of estrogen ($E_2$) treatment and function of estrogen receptor alpha ($ER{\alpha}$) and estrogen receptor beta ($ER{\beta}$) on telomerase activity were investigated in human mesenchymal stem cells (hMSCs). Telomerase activity and mRNA expression of the catalytic subunit of telomerase (hTERT) were upregulated by treatment of the cells with $E_2$. The protein concentration of $ER{\alpha}$ was also increased by $E_2$ treatment, and enhancement of $ER{\alpha}$ accumulation in the nucleus was clearly detected with immunocytochemistry. When $ER{\alpha}$ expression was reduced by siRNA transfection into hMSCs, the effect of $E_2$ on the induction of hTERT expression and telomerase activity was diminished. In contrast, the transient overexpression of $ER{\alpha}$ increased the effect of $E_2$ on the expression of hTERT mRNA. These findings indicate that the activation of hTERT expression and telomerase activity by $E_2$ in hMSCs depends on $ER{\alpha}$, but not on $ER{\beta}$.

• 한국수정란이식학회지
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• 제32권2호
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• pp.39-45
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• 2017

Mesenchymal stem cells (MSCs) have been considered an alternative source of neuronal lineage cells, which are difficult to isolate from brain and expand in vitro. Previous studies have reported that MSCs expressing Nestin ($Nestin^+$ MSCs), a neuronal stem/progenitor cell marker, exhibit increased transcriptional levels of neural development-related genes, indicating that $Nestin^+$ MSCs may exert potential with neurogenic differentiation. Accordingly, we investigated the effects of the presence of $Nestin^+$ MSCs in bone-marrow-derived primary cells (BMPCs) on enhanced neurogenic differentiation of BMPCs by identifying the presence of $Nestin^+$ MSCs in uncultured and cultured BMPCs. The percentage of $Nestin^+$ MSCs in BMPCs was measured per passage by double staining with Nestin and CD90, an MSC marker. The efficiency of neurogenic differentiation was compared among passages, revealing the highest and lowest yields of $Nestin^+$ MSCs. The presence of $Nestin^+$ MSCs was identified in BMPCs before in vitro culture, and the highest and lowest percentages of $Nestin^+$ MSCs in BMPCs was observed at the third (P3) and fifth passages (P5). Moreover, significantly the higher efficiency of differentiation into neurons, oligodendrocyte precursor cells and astrocytes was detected in BMPCs at P3, compared with P5. In conclusion, these results demonstrate that neurogenic differentiation can be enhanced by increasing the proportion of $Nestin^+$ MSCs in cultured BMPCs.

• Molecules and Cells
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• 제37권2호
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• pp.161-171
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• 2014

In several lysosomal storage disorders, including Niemann-Pick disease Type C (NP-C), sphingolipids, including glycosphingolipids, particularly gangliosides, are the predominant storage materials in the brain, raising the possibility that accumulation of these lipids may be involved in the NP-C neurodegenerative process. However, correlation of these accumulations and NP-C neuropathology has not been fully characterized. Here we derived NP-C mice with complete and partial deletion of the Siat9 (encoding GM3 synthase) gene in order to investigate the role of ganglioside in NP-C pathogenesis. According to our results, NP-C mice with homozygotic deletion of GM3 synthase exhibited an enhanced neuropathological phenotype and died significantly earlier than NP-C mice. Notably, in contrast to complete depletion, NP-C mice with partial deletion of the GM3 synthase gene showed ameliorated NP-C neuropathology, including motor disability, demyelination, and abnormal accumulation of cholesterol and sphingolipids. These findings indicate the crucial role of GM3 synthesis in the NP-C phenotype and progression of CNS pathologic abnormality, suggesting that well-controlled inhibition of GM3 synthesis could be used as a therapeutic strategy.

• The Korean Journal of Pain
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• 제11권1호
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• pp.23-29
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• 1998

Background: The present study was conducted to investigate effects of microinjection of bicuculline, GABA-A receptor antagonist, into the brain stem nuclei on the dorsal horn neuron responsiveness in rats with an experimental peripheral neuropathy. Methods: An experimental neuropathy was induced by a unilateral ligation of L5~L6 spinal nerves of rats. After 2~3 weeks after the surgery, single-unit recording was made from wide dynamic range (WDR) neurons in the spinal cord dorsal horn. Results: Responses of WDR neurons to both noxious and innocuous mechanical stimuli applied to the somatic receptive fields were enhanced on the nerve injured side. These enhanced responsiveness of WDR neurons were suppressed by microinjection of bicuculline into periaqueductal gray(PAG) or nucleus reticularis gigantocellularis(Gi). A similar suppression was also observed when morphine was microinjected into PAG or Gi. Suppressive action by Gi-bicuculline was reversed by naloxonazine, ${\mu}$-opioid receptor antagonist, microinjected into PAG whereas PAG-bicuculline induced suppression was not affected by naloxonazine injection into Gi. Gi-bicuculline induced suppression were reversed by a transection of dorsolateral funiculus(DLF) of the spinal cord. Conclusions: The results suggest that endogenous opioids, via acting on GABAergic interneurons in PAG and Gi, may be involved in the control of neuropathic pain by activating the descending inhibitory pathways that project to the spinal dorsal horn through DLF to inhibit the responsiveness of WDR neurons.

• 대한기관식도과학회:학술대회논문집
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• 대한기관식도과학회 1991년도 제25차 학술대회 연제순서 및 초록
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• pp.14-14
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• 1991

후두의 생리적 기능은 하기도를 보호하는 방어기능과 호흡기능 그리고 발성기능으로 대별할 수 있는데 이 가운데 계통발생적으로 가장 원시적이지만 중요한 기능은 하기도 방어기능으로 이는 다른 기능과 달리 전적으로 불수의적이고 반사적으로 이루어진다. 이 기능은 후두내 점막에 존재하는 촉각 수용체(tactile receptor)가 자극되면서 후두근육이 수축 반사를 일으켜 성문이 닫히는 성문폐쇄반사(glottic closure reflex)로서 다접합뇌간반사(polysynaptic brain stem response)이다. 현재까지 후두의 신경장애에서 그 부위나 정도 또는 신경재생 상태 등을 검사하는 방법으로 근전도검사가 주로 쓰여져 왔으나 그것이 주는 정보가 극히 제한되어 있다. 그러나 최근 청각뇌간유발반응과 같이 후두뇌간유발반응 이라 명명된 wave가 존재한다는 사실이 밝혀져 이에 대한 연구가 이루어지고 있어 이것이 임상에 쓰여질 수 있다면 현재 성문폐쇄반사의 소실이나 이상이 원인으로 사료되는 idiopathic laryngospasm, gastroesophageal reflux, spastic dysphonia, stuttering, sudden infant death syndrome과 같은 질환의 진단과 치료에 커다란 진전이 있을 것이다. 이에 저자들은 고양이 6마리를 이용하여 상후두신경을 전기적으로 자극하여 유발되는 반응을 far field recording을 이용 평균 가산법으로 그 wave를 측정하여 다음과 같은 결과를 얻었다. 1. 상후두신경자극(2㎃, stimuli frequency 3/s, Band filter 320-1000, 0.2 ㎳ duration)에 의한 반회신경에의 유발 반응을 기록하였고 그 잠복시간은 평균 8.2 ㎳ 였다. 2. 상후두신경을 자극하여 후두뇌간유발반응을 기록하였고 후두뇌간유발반응은 4개의 양 wave와 4개의 음 wave로 구성되었다. 3. 각 wave의 평균 잠복시간은 P1은 0.8㎳, P2는 2.3㎳, P3는 3.6㎳, P4는 4.3㎳였고 N1은 1.5㎳, N2 은 2.7㎳, N3는 3.9㎳, N4는 5.5㎳ 였다.

• BMB Reports
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• 제56권9호
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• pp.520-525
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• 2023

Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by cognitive decline. Several recent studies demonstrated that impaired adult neurogenesis could contribute to AD-related cognitive impairment. Adult subventricular zone (SVZ) neurogenesis, which occurs in the lateral ventricles, plays a crucial role in structural plasticity and neural circuit maintenance. Alterations in adult SVZ neurogenesis are early events in AD, and impaired adult neurogenesis is influenced by the accumulation of intracellular Aβ. Although Aβ-overexpressing transgenic 5XFAD mice are an AD animal model well representative of Aβ-related pathologies in the brain, the characterization of altered adult SVZ neurogenesis following AD progression in 5XFAD mice has not been thoroughly examined. Therefore, we validated the characterization of adult SVZ neurogenesis changes with AD progression in 2-, 4-, 8-, and 11-monthold male 5XFAD mice. We first investigated the Aβ accumulation in the SVZ using the 4G8 antibody. We observed intracellular Aβ accumulation in the SVZ of 2-month-old 5XFAD mice. In addition, 5XFAD mice exhibited significantly increased Aβ deposition in the SVZ with age. Next, we performed a histological analysis to investigate changes in various phases of adult neurogenesis, such as quiescence, proliferation, and differentiation, in SVZ. Compared to age-matched wild-type (WT) mice, quiescent neural stem cells were reduced in 5XFAD mice from 2-11 months of age. Moreover, proliferative neural stem cells were decreased in 5XFAD mice from 2 to 8 months of age. Furthermore, differentiations of neuroblasts were diminished in 5XFAD mice from 2-11 months of age. Intriguingly, we found that adult SVZ neurogenesis was reduced with aging in healthy mice. Taken together, our results revealed that impairment of adult SVZ neurogenesis appears with aging or AD progression.

• Journal of Korean Neurosurgical Society
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• 제29권1호
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• pp.5-14
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• 2000

Objective : Somatosensory evoked potential(SSEP) has been known to be a good method for evaluating brain stem function, but it is not sufficient to check the fine changes of cortical functions. A fine change of cortical function can be expressed with somatosensory evoked cortical field potential(SSEFP) rather than general SSEP. To confirm the usefulness of SSEFP for evaluating the cortical function, the authors simultaneously measured SSEFP and the intracranial pressure-volume index(PVI) in kaolin-induced hydrocephalic rats. Method : Hydrocephalus was induced with injection of 0.1ml kaolin-suspended solution into the cisterna magna in 60 Sprague-Dawley rats. The authors measured PVI and SSEFP 1 week after injection of kaolin-suspended solution. To evaluate the severity of induced hydrocephalus, we measured the transverse diameter of the lateral ventricle on the coronal slice of the rat brain 0.40mm posterior to the bregma. Result : The typical wave form of SSEFP in control rats showed a negative-positive complex wave at early latency. In SSEFP of normal rats, N0 is 10.0 msec, N1 15.3 msec, P1 31.2 msec and N1-P1 amplitude $15.4{\mu}V$. As hydrocephalus progressed, the peak latency of N1 and P1 were delayed. In mild hydrocephalus, negative peak waves were split. The N1-P1 amplitude was decreased only in severe hydrocephalus. The changes of the characteristics of SSEFP according to the severity of hydrocephalus were well correlated with the changes of PVI. Shunting normalized the characteristics of SSEFP in relation to ventricular sizes and PVI in hydrocephalic rats. Conclusion : SSEFP may be useful for evaluating the impairment of cortical function in hydrocephalus.