Postnatal Development of Subcallosal Zone Following Suppression of Programmed Cell Death in Bax-deficient Mice

김운령,선웅 한국발생생물학회 2013 발생과 생식 Vol.17 No.3

Neural stem cells are found in adult mammalian brain regions including the subgranular zone (SGZ) of the dentate gyrus (DG) and the subventricular zone (SVZ). In addition to these two regions, other neurogenic regions are often reported in many species. Recently, the subcallosal zone (SCZ) has been identified as a novel neurogenic region where new neuroblasts are spontaneously generated and then, by Bax-dependent apoptosis, eliminated. However, the development of SCZ in the postnatal brain is not yet fully explored. The present study investigated the precise location and amount of neuroblasts in the developing brain. To estimate the importance of programmed cell death (PCD) for SCZ histogenesis, SCZ development in the Bax-knockout (KO) mouse was examined. Interestingly, an accumulation of extra neurons with synaptic fibers in the SCZ of Bax-KO mice was observed. Indeed, Bax-KO mice exhibited enhanced startle response to loud acoustic stimuli and reduced anxiety level. Considering the prevention of PCD in the SCZ leads to sensory-motor gating dysfunction in the Bax-KO mice, active elimination of SCZ neuroblasts may promote optimal brain function.

Polarized and Stage-Dependent Distribution of Immunoreactivity for Novel PDZ-Binding Protein Preso1 in Adult Neurogenic Regions

이은수,김운령,김영화,이현우,김현,선웅 대한내분비학회 2014 Endocrinology and metabolism Vol.29 No.3

Background: Adult neural stem cells have the potential for self-renewal and differentiation into multiple cell lineages via symmetric or asymmetric cell division. Preso1 is a recently identified protein involved in the formation of dendritic spines and the promotion of axonal growth in developing neurons. Preso1 can also bind to cell polarity proteins, suggesting a potential role for Preso1 in asymmetric cell division. Methods: To investigate the distribution of Preso1, we performed immunohistochemistry with adult mouse brain slice. Also, polarized distribution of Preso1 was assessed by immunocytochemistry in cultured neural stem cells. Results: Immunoreactivity for Preso1 (Preso1-IR) was strong in the rostral migratory stream and subventricular zone, where proliferating transit-amplifying cells and neuroblasts are prevalent. In cultured neural stem cells, Preso1-IR was unequally distributed in the cell cytosol. We also observed the distribution of Preso1 in the subgranular zone of the hippocampal dentate gyrus, another neurogenic region in the adult brain. Interestingly, Preso1-IR was transiently observed in the nuclei of doublecortin-expressing neuroblasts immediately after asymmetric cell division. Conclusion: Our study demonstrated that Preso1 is asymmetrically distributed in the cytosol and nuclei of neural stem/progenitor cells in the adult brain, and may play a significant role in cell differentiation via association with cell polarity machinery.

만성스트레스 우울증 동물 모델에서 경두개자기자극이 해마 시냅스 가소성에 미치는 영향

김은주,김운령,이연경,최준식,박은혜,김현택,박순권 한국인지및생물심리학회 2006 한국심리학회지 인지 및 생물 Vol.18 No.4

Despite its therapeutic success in treating major depression, little is known about the mechanism by which repetitive transcranial magnetic stimulation (rTMS) alters physiological responses of neurons. To elucidate cellular processes underlying rTMS, we compared the effect of rTMS on hippocampal long-term potentiation (LTP) with those of electroconvulsive shock (ECS) and fluoxetine. Male Wistar rats were subjected to chronic mild stress (CMS) regimen, an animal model of depression, for six weeks. Anhedonia, a behavioral symptom of depression, was tested by measuring sucrose consumptions. There was a significant difference in sucrose intake between nave and CMS-exposed animals. The rats were then treated with one of the three conditions: rTMS (rTMS), sham rTMS (SHAM), ECS (ECS), or fluoxetine (FLX) for two weeks. Following two weeks of treatments with rTMS, sham rTMS, ECS, or fluoxetine, they were anesthetized and LTP was induced in vivo in the perforant path-dentate gyrus synapses. Field excitatory postsynaptic potentials (fEPSP) were monitored for 50 min after the LTP induction. LTP induction was impaired in CMS (sham rTMS) and FLX group compared to the nave control group. The potentiated fEPSP of the ECS group was marginally different from that of NAVE group, showing a trend toward impaired LTP. On the other hand, LTP was recovered to the level of nave animals in rats treated with rTMS. These results suggest that rTMS has a rescuing effect on electrophysiological properties of the hippocampal neurons by reversing the impaired synaptic efficacy caused by the CMS procedure and that the antidepressant effect of rTMS might be mediated by its protective action on the synaptic plasticity. 경두개자기자극(repetitive transcranial magnetic stimulation: rTMS)은 최근 주요우울증 치료에 이용될 수 있는 가능성이 대두되고 있으나, 이 자극이 작용하는 세포 수준에서의 생리학적 기전은 아직 거의 알려져 있지 않다. 본 연구에서는 rTMS의 작용기전을 세포 수준에서 알아보기 위해 rTMS가 동물의 전기생리학적 변화에 미치는 영향을 검사하였고, 이 효과를 우울증의 전통적 자극 기법인 전기경련충격(electroconvulsive shock: ECS)과 항우울제 중 하나인 fluoxetine과 비교하여 보았다. 수컷 Wistar 쥐를 우울증 동물 모델인 경미한 만성스트레스 (chronic mild stress: CMS) 모델에 6주 동안 노출시켰고, 동물이 자당용액을 섭취하는 양을 측정하여 우울증의 행동적 증상인 무쾌감증(anhedonia)을 검사하였다. CMS에 노출된 동물과 비처치 집단 (NAIVE)의 동물 사이에 자당용액 섭취량에서 통계적으로 유의한 차이가 나타났다. 무쾌감증을 확인한 후, CMS에 노출되었던 동물을 다음의 네 집단으로 나누어 2주 동안 CMS와 함께 처치하였다: rTMS 처치집단(rTMS), 모의 rTMS 처치집단 (SHAM), ECS 처치집단(ECS), fluoxetine 처치집단(FLX). 2주간의 각 처치가 종결된 후, 동물을 마취하여 관통로-치상핵 시냅스에서 장기상승작용(long term potentiation: LTP)을 in vivo로 유도하였고, 흥분성 시냅스후 장전위 (fEPSP)를 기록하였다. NAIVE 집단에 비하여 SHAM 집단과 FLX 집단에서는 LTP가 거의 유도되지 않았다. 그러나, rTMS를 처치한 쥐에서는 LTP가 NAIVE 집단의 수준을 보여 LTP 손상이 일어나지 않은 것을 확인하였다. rTMS 집단에서 LTP 손상이 일어나지 않은 것에 반해, ECS 집단에서는 LTP의 감소 경향이 있었으며, NAIVE 동물과 통계적으로 경미한 차이를 보였다. 이러한 결과는 rTMS가 CMS 처치에 의해 야기될 수 있는 시냅스 효율성의 손상을 보호함으로써 해마 뉴런의 정상적인 전기생리학적 현상을 손상시키지 않으며, rTMS의 항우울 효과는 이러한 시냅스 가소성의 보호 효과를 매개로 할 가능성이 있음을 시사한다.

우울증모델 흰쥐에 대한 죽여와 St. john's Wort의 항우울효과에 대한 비교 연구

박세진,황의완,김현택,지상은,김운령,김종우 대한한방신경정신과학회 2004 동의신경정신과학회지 Vol.15 No.2

Objective : This study was designed to assess the protective effects of Bambusae caulis and St. John's Wort on the animal model of depression, induced by chronic mild stress(CMS)Method : Male Wistar rats were used for this experiment. The subjects were divided into 4 groups ( 1. CMS-drugs: Bambusae caulis administered during CMS treatment, 2. CMS-drugs: St. John's Wort administered during CMS treatment, 3. CMS-vehicle: Water administered during CMS treatment, 4. normal control group without CMS treatment ). After 3 weeks of CMS treatment, they were executed open field test and weight, sucrose intake were measured.Result : 1. CMS Bambusae caulis group showed significant difference of locomotor activities and marginal difference of start latency in comparison with other groups in open field test.2. There was no change of weights between CMS Bambusae caulis, St. John's Wort groups and CMS control group.3. CMS St. John's Wort group showed upper level of sucrose intake than CMS Bambusae caulis group and CMS control group.Conclusion : These results suggest that Bambusae caulis may have protective antidepressant effects in CMS model rats. And these effects could be explained by the elevated locomotor activities in open field test.

Different expression of human GFAP promoter-derived GFP in different subsets of astrocytes in the mouse brain

문영혜,김현정,김주연,김현,김운령,선웅 한국통합생물학회 2011 Animal cells and systems Vol.15 No.4

Transgenic mice expressing green fluorescent protein (GFP) under the control of human glial fibrillary acidic protein promoter (hGFAP) have been utilized for in vivo labeling of astrocytes. Although it has been considered that virtually all astrocytes express GFP in this transgenic mouse, we found that different subsets of GFAP-expressing astrocytes express considerably different levels of GFP in the adult brain. Astrocytes in the spinal cord, the molecular layer of thecerebellum, meninges, white matter, corpus callosum and blood vessels exhibited strong GFP, whereas subsets of astrocytes associated with granule cells in the cerebellum and dentate gyrus did not or only marginally exhibited GFP. We also found that a small subset of GFP-expressing cells in the periglomeruli of the olfactory bulb did not express GFAP immunoreactivity. Collectively, these results suggest that human GFAP promoter-derived GFP expression does not faithfully recapitulate the endogenous GFAP expression in mice, suggesting that upstream regulatory mechanisms controlling GFAP transcription are different in different populations of astrocytes, and may reflect the functional diversity of astrocytes.

CDK5-dependent inhibitory phosphorylation of Drp1 during neuronal maturation

조봉기,조효민,김현정,정재훈,박상기,황은미,박재용,김운령,김현,선웅 생화학분자생물학회 2014 Experimental and molecular medicine Vol.46 No.-

Mitochondrial functions are essential for the survival and function of neurons. Recently, it has been demonstrated that mitochondrial functions are highly associated with mitochondrial morphology, which is dynamically changed by the balance between fusion and fission. Mitochondrial morphology is primarily controlled by the activation of dynamin-related proteins including dynamin-related protein 1 (Drp1), which promotes mitochondrial fission. Drp1 activity is regulated by several posttranslational modifications, thereby modifying mitochondrial morphology. Here, we found that phosphorylation of Drp1 at serine 616 (S616) is mediated by cyclin-dependent kinase 5 (CDK5) in post-mitotic rat neurons. Perturbation of CDK5 activitymodified the level of Drp1S616 phosphorylation and mitochondrial morphology in neurons. In addition, phosphorylated Drp1S616 preferentially localized as a cytosolic monomer compared with total Drp1. Furthermore, roscovitine, a chemical inhibitor of CDKs, increased oligomerization and mitochondrial translocation of Drp1, suggesting that CDK5-dependent phosphorylation of Drp1 serves to reduce Drp1’s fission-promoting activity. Taken together, we propose that CDK5 has a significant role in the regulation of mitochondrial morphology via inhibitory phosphorylation of Drp1S616 in post-mitotic neurons.

우울증(憂鬱症)모델 흰쥐에 대한 죽여(竹茹)와 St. John`s Wort의 항우울효과(抗憂鬱效果)에 대한 비교 연구

박세진 ( Se Jin Park ),김종우 ( Jong Woo Kim ),황의완 ( Ui Wan Hwang ),김현택 ( Hyun Taek Kim ),지상은 ( Sang Eun Chi ),김운령 ( Wonn Ryoung Kim ) 대한한방신경정신과학회 2004 동의신경정신과학회지 Vol.15 No.2

우울증(憂鬱症) 모델 흰쥐에 대한 조위승청탕(調胃升淸湯)과 St. John`s Wort의 항우울효과(抗憂鬱效果)에 관한 비교 연구

김경욱 ( Kim Kyung Ook ),황의완 ( Hwang Ui Wan ),김종우 ( Kim Jong Woo ),김현택 ( Kim Hyun Taek ),지상은 ( Chi Sang Eun ),김운령 ( Kim Woon Ryoung ) 대한한방신경정신과학회 2004 동의신경정신과학회지 Vol.15 No.1