생쥐 대뇌겉질의 발생단계별 Synaptophysin 발현량 차이에 관한 연구

편희장(Hee-Jang Pyeon),이영일(Young-Ill Lee) 대한체질인류학회 2012 대한체질인류학회지 Vol.25 No.1

신경연접(neural synapse)의 형성은 신경세포 사이의 전기적 신호전달 시작을 의미하므로 신경세포의 분화와 더불어 중추신경계의 발생 및 성장에 매우 중요한 단계라 할 수 있다. 본 연구는 생쥐(mouse)의 대뇌겉질(cerebral cortex)에서 신경 연접표지 인자(synaptoeenic marker) 중의 하나인 synaptophysin의 발현양상 및 그 양적 차이를 대뇌겉질의 발달단계에 따라 층별로 비교분석하여 각각의 특징을 밝혀내는 것을 목적으로 진행되었다. 이를 위해 본 연구에서는 synaptophysin에 대한 면역형광염색을 하였으며, 최종적으로 소프트웨어를 활용한 형태학적 정량를 시행하였다. 배아(embryo)와 신생(neonate) 생쥐의 synaptophysin 발현은 대뇌겉질의 얕은층(superficial layer)보다 깊은층(deep layer)에서 더 높게 나타났으며 통계적으로 유의한 차이를 보였다. 또한 분자층(molecular layer)에 해당하는 부위에서도 상대적으로 많이 발현되는 것이 확인되었다. 대뇌겉질의 깊은층에서 synaptophysin 발현의 유의한 증가는 주로 배아기에 국한되어 나타났으며, 이후 층 사이의 synaptophysin 발현 차이는 점차 감소하여 성숙한 생쥐에서는 차이가 없었다. 연구결과, 대뇌겉질에서 신경연접의 형성은 중추신경계의 성장단계에 따라 층별로 다르게 나타남을 알 수 있다. 이는 신경연접형성과 관련된 중추신경계의 부위별 특징을 파악하고 나아가 중추신경계의 발달과정에서 나타나는 다양한 병태생리를 이해하는 데 도움을 줄 것으로 기대한다. It is well known that differentiation and growth of central nervous system are accomplished through relatively early stages of development. The formation of neural synapse indicates beginning of electrical signaling between neurons, so that may be a critical step in the differentiation of neurons as well as the development and growth of central nervous system. The purpose of this study was to investigate the differential expression levels and patterns of synaptic marker(synaptophysin) between superficial and deep layers of cerebral cortex according to the developmental stages. We introduced immunofluorescence staining of synaptophysin combined with densitometric analysis for the morphological quantification. The intensities of synaptophysin immuno-reactivities in deep layers of cerebral cortices were significantly higher compared to superficial layers in cerebral cortices of embryonic and neonatal mice. The significant increase of synaptophysin expression in the deep layer of cerebral cortex was mainly confined to the embryonic stage. As the expression of synaptophysin gradually decrease thereafter, the difference of expression level between superficial and deep layers could not find in the adult mice. From this study, we could confirm indirectly through synaptophysin that synaptogenic activities in the deep layer of cerebral cortex shows unique pattern especially during the early stages of brain development. Results from this study will be helpful for understanding different patterns of synaptogenesis among the various regions of developing brain.

추간판의 퇴행성 변화에 따른 신경섬유의 분포 및 변화

양준영,이준규,최의성,이현호,우세민,이정범 대한척추외과학회 2004 대한척추외과학회지 Vol.11 No.1

뇌종양에서 Synaptophysin 발현이 진단적 의의 재평가

최병하,강신광 대한병리학회 2001 Journal of Pathology and Translational Medicine Vol.35 No.4

Differential expression levels of synaptophysin through developmental stages in hippocampal region of mouse brain

Hee-Jang Pyeon,Young-Il Lee 대한해부학회 2012 Anatomy & Cell Biology Vol.45 No.2

The formation of neural synapses according to the development and growth of neurite were usually studied with various markers. Of these markers, synaptophysin is a kind of synaptic protein located in the synaptic vesicle of neuron or neuroendocrine cell known to be distributed consistently in all neural synapses. The purpose of this study was to investigate differential expression levels and patterns of synaptic marker (synaptophysin) in the mouse hippocampal region according to the developmental stages of embryonic, neonatal, and adulthood respectively. In the embryonic and neonatal groups, synaptophysin immunofluorescence was almost defined to cornu ammonis subfields (CA1 and CA3) of hippocampus and subiculum proper in the hippocampal region. However in dentate gyrus, synaptophysin immunoreactivities were insignificant or absent in all developmental stages. In embryonic and neonatal hippocampus, the intensities of immuneuorescence were significantly different between molecular and oriens layers. Furthermore, those intensities were decreased considerably in both layers of neonatal group compared to embryonic. The results from this study will contribute to characterizing synaptogenic activities in the central nervous system through developmental stages.

Effects of Cumene Exposure on Synaptophysin and GFAP Expressions in Hippocampus of Rat

Kyoung-Youl Lee,Eun-Sang Cho,Min-Gu Kang,Sung-Bae Lee,Hyeon-Yeong Kim,Hwa-Young Son 한국실험동물학회 2009 Laboratory Animal Research Vol.25 No.4

Cumene, a widely used organic solvent, decreases neuronal activity and depresses behavior in both animals and humans. However there are little known about their mechanisms on neuronal toxicity. Hippocampus, one of the limbic areas associated with learning and memory functions, is vulnerability to excitotoxicity. We investigated the effect of acute and subacute exposure of cumene on expressions of synaptophysin and glial fibrillary acidic protein (GFAP) in the hippocampi. Synaptophysin a neuronal marker of synaptogenesis, has been implicated in disorders of neurodevelopment, and GFAP a crucial role in neuronal survival is a peripheral marker of neurodegeneration. SD male rats were exposed to cumene (0, 8, 80, and 800 ppm) by inhalation chamber for 1, 14, 28, and 90 days. In Western blot analysis, the expression levels of synaptophysin in the hippocampi were significantly increased at 800 ppm on day 14 and significantly decreased at 8 ppm on day 28. Meanwhile, levels of GFAP were significantly increased in hippocampi at 1, 14 and 28 days after cumene exposure when compared to the control group. We found that cumene inhalation could effect on the expression of synaptophysin and GFAP in hippocampus, even dose of 8 ppm. These findings suggest that acute and subacute exposure of cumene may contribute to neuronal dysfunction and degeneration in rat hippocampus.

Glial Cell Line-Derived Neurotrophic Factor, S-100 Protein and Synaptophysin Expression in Biliary Atresia Gallbladder Tissue

Gurunluoglu, Semra,Ceran, Canan,Gurunluoglu, Kubilay,Kocbiyik, Alper,Gul, Mehmet,Yildiz, Turan,Bag, Harika Gozukara,Gul, Semir,Tasci, Aytac,Bayrakci, Ercan,Akpinar, Necmettin,Cin, Ecem Serbest,Ates, H The Korean Society of Pediatric Gastroenterology 2021 Pediatric gastroenterology, hepatology & nutrition Vol.24 No.2

Purpose: Biliary atresia (BA) is a disease that manifests as jaundice after birth and leads to progressive destruction of the ductal system in the liver. The aim of this study was to investigate histopathological changes and immunohistochemically examine the expression of glial cell line-derived neurotrophic factor (GDNF), synaptophysin, and S-100 protein in the gallbladder of BA patients. Methods: The study included a BA group of 29 patients and a control group of 41 children with cholecystectomy. Gallbladder tissue removed during surgery was obtained and examined immunohistochemically and histopathologically. Tissue samples of both groups were immunohistochemically assessed in terms of GDNF, S-100 protein, and synaptophysin expression. Expression was classified as present or absent. Inflammatory activity assessment with hematoxylin and eosin staining and fibrosis assessment with Masson's trichrome staining were performed for tissue sample sections of both groups. Results: Ganglion cells were not present in gallbladder tissue samples of the BA group. Immunohistochemically, GDNF, synaptophysin, and S-100 expression was not detected in the BA group. Histopathological examination revealed more frequent fibrosis and slightly higher inflammatory activity in the BA than in the control group. Conclusion: We speculate that GDNF expression will no longer continue in this region, when the damage caused by inflammation of the extrahepatic bile ducts reaches a critical threshold. The study's findings may represent a missing link in the chain of events forming the etiology of BA and may be helpful in its diagnosis.

대장과 직장의 신경내분비암종

김동훈,이우용,윤해란,최영철,조용범,윤성현,김희철,전호경 대한대장항문학회 2009 Annals of Coloproctolgy Vol.25 No.1

Purpose: The aim of this study was to review our experience with neuroendocrine carcinoma (NEC) of the colon and rectum to highlight the clinical and pathological characteristics in this relatively uncommon malignancy. Methods: From December 1995 to December 2006, 11 patients with NEC were identified from our database of 6,143 colorectal cancer patients (0.18%), which does not include carcinoid tumors. The pathology was retrospectively reviewed and the tumors were categorized as pure NEC, including well-differentiated NEC (n=3), poorly-differentiated (n=3) and mixed endocrine/ exocrine tumor (n=5) on the basis of the histology and immunohistochemical findings. Results: The mean age of the patients was 57 yr (range, 37 to 69 yr). The tumors were located as follows: 8 in the colon and 3 in the rectum. The diagnosis of NEC was suggested preoperatively from the tissue biopsy in 2 of 9 patients (22.2%). The tumors were advanced at the time of diagnosis, with American Joint Committee on Cancer Stage III (n=7) and Stage IV disease (n=4). Most tumors stained positive by immunohistochemistry for neuroendocrine markers, including synaptophysin (7/9, 77.8%); however, chromogranin was expressed in 4 of 9 NEC tumors (44.4%). Metastatic disease was detected at the time of diagnosis in 36.4% (4/11) of the patients. The median survival for NEC was 16 mo (3.6-67.4 mo), and for pure NEC and mixed endocrine/exocrine tumor was 4.1 mo and 23.6 mo, respectively. Conclusion: NEC had distinctive cytoarchitectural features and was often immunoreactive for neuroendocrine markers. Our findings showed that pure NEC had aggressive behavior and a poor prognosis. Purpose: The aim of this study was to review our experience with neuroendocrine carcinoma (NEC) of the colon and rectum to highlight the clinical and pathological characteristics in this relatively uncommon malignancy. Methods: From December 1995 to December 2006, 11 patients with NEC were identified from our database of 6,143 colorectal cancer patients (0.18%), which does not include carcinoid tumors. The pathology was retrospectively reviewed and the tumors were categorized as pure NEC, including well-differentiated NEC (n=3), poorly-differentiated (n=3) and mixed endocrine/ exocrine tumor (n=5) on the basis of the histology and immunohistochemical findings. Results: The mean age of the patients was 57 yr (range, 37 to 69 yr). The tumors were located as follows: 8 in the colon and 3 in the rectum. The diagnosis of NEC was suggested preoperatively from the tissue biopsy in 2 of 9 patients (22.2%). The tumors were advanced at the time of diagnosis, with American Joint Committee on Cancer Stage III (n=7) and Stage IV disease (n=4). Most tumors stained positive by immunohistochemistry for neuroendocrine markers, including synaptophysin (7/9, 77.8%); however, chromogranin was expressed in 4 of 9 NEC tumors (44.4%). Metastatic disease was detected at the time of diagnosis in 36.4% (4/11) of the patients. The median survival for NEC was 16 mo (3.6-67.4 mo), and for pure NEC and mixed endocrine/exocrine tumor was 4.1 mo and 23.6 mo, respectively. Conclusion: NEC had distinctive cytoarchitectural features and was often immunoreactive for neuroendocrine markers. Our findings showed that pure NEC had aggressive behavior and a poor prognosis.

Malignant Retroperitoneal Paraganglioma in a Siberian Tiger

신상경,박병민,염소영,김태왕,나기정,안병우 한국임상수의학회 2011 한국임상수의학회지 Vol.28 No.5

A 14 year old female Siberian tiger presented for postmortem examination. A large mass attached to sublumbar area was found to be circumscribing aorta with metastases to mesenteric lymph nodes, uterus, kidney, adrenal gland, lung and thymus. The tumor cells were arranged in clusters or nests separated by well-developed fibrovascular stroma. The individual cells were plump and polygonal with granular eosinophilic cytoplasms and had distinct cell borders. The tumor cells were positive for synaptophysin, chromogranin A and neuron-specific enolase, and negative for cytokeratins, S100 and glial fibrillary acidic protein. The primary tumor was diagnosed as a malignant retroperitoneal paraganglioma.

Early Motor Balance and Coordination Training Increased Synaptophysin in Subcortical Regions of the Ischemic Rat Brain

서한길,김대열,박희원,이시욱,박성혜 대한의학회 2010 Journal of Korean medical science Vol.25 No.11

The aim of this study was to evaluate the effect of early motor balance and coordination training on functional recovery and brain plasticity in an ischemic rat stroke model,compared with simple locomotor exercise. Adult male Sprague-Dawley rats with cortical infarcts were trained under one of four conditions: nontrained control, treadmill training,motor training on the Rota-rod, or both Rota-rod and treadmill training. All types of training were performed from post-operation day 1 to 14. Neurological and behavioral performance was evaluated by Menzies’ scale, the prehensile test, and the limb placement test, at post-operation day 1, 7, and 14. Both Rota-rod and treadmill training increased the expression of synaptophysin in subcortical regions of the ischemic hemisphere including the hippocampus, dentate gyrus, and thalamus, but did not affect levels of brain-derived neurotrophic factor or tyrosin kinase receptor B. The Rota-rod training also improved Menzies’ scale and limb placement test scores, whereas the simple treadmill training did neither. The control group showed significant change only in Menzies’ scale score. This study suggests that early motor balance and coordination training may induce plastic changes in subcortical regions of the ischemic hemisphere after stroke accompanied with the recovery of sensorimotor performance.

대장 신경내분비종양의 임상 경과와 병리 특징

정상훈 ( Sang Hun Jung ),김희철 ( Hee Cheol Kim ),유창식 ( Chang Sik Yu ),장흥문 ( Heung Moon Chang ),류민희 ( Min Hee Ryu ),이재련 ( Jae Lyun Lee ),김정선 ( Jung Sun Kim ),김진천 ( Jin Cheon Kim ) 대한소화기학회 2006 대한소화기학회지 Vol.48 No.2

목적: 대장의 신경내분비종양은 매우 드물고, 통상적인 대장암에 비해 빠르게 진행하며 예후가 매우 나쁘다. 그러나 발생 빈도가 적어 국내에는 아직까지 보고가 없다. 이번 연구는 후향 분석을 통해 대장의 신경내분비종양의 임상 경과 및 병리 특징을 알고자 하였다. 대상 및 방법: 1997년 6월부터 2004년 12월까지 서울아산병원에서 H&E 및 면역조직화학염색에 의해 조직학적으로 대장의 신경내분비종양으로 진단 받은 13예의 환자를 대상으로 하였으며, 대장의 신경내분비암종 10예와 대장의 샘암종에 신경내분비분화를 포함하는 혼합암종이 3예였다. 카르시노이드 종양은 대상에서 제외되었으며, 환자들의 기록은 후향으로 조사하였다. 결과: 4,512명 중 13예(0.3%)의 환자가 대장의 신경내분비종양으로 진단되었다(신경내분비암종 10예, 혼합암종 3예). 환자 나이의 중앙값은 60세(41-83세)였으며, 남자가 6예, 여자는 7예였다. 종양의 발생부위는 직장 9예, 에스자결장 2예, 그리고 맹장과 횡행결장이 각각 1예였다. 면역조직화학염색을 시행한 신경내분비암종 9예 모두 synaptophysin 양성인 반면, chromogranin A는 3예에서 양성이었다. 6차 AJCC TNM병기에 따라 IIIB 병기 2예, IIIC 병기 3예 그리고 IV 병기가 8예였으며, 대장의 신경내분비암종 환자에서는 10예 중 7예에서 원격전이가 있었다. 신경내분비암종 10예와 혼합암종 3예의 중간생존율은 각각 16.4개월과 30개월이었다. 10예의 신경내분비암종 환자 중 항암치료를 받은 5예의 중간생존율은 III 병기 3예와 IV 병기 2예에서 각각 32개월과 17.5개월이었으나, 항암치료를 받지 않은 5예의 중간생존율은 6.2개월이었다. 혼합암종 3예는 모두 항암치료를 받았으며 중간생존율은 30개월이었다. 결론: 대장의 신경내분비종양의 빈도는 0.3%로 매우 드물다. 지금까지 적은 수의 환자와 빠르게 진행되는 종양의 특성으로 유용한 치료방침이 없었으나, 적극적인 병소의 절제와 etoposide/cisplatin을 이용한 항암치료 및 방사선치료는 환자의 생존율을 향상시킬 수 있을 것으로 기대한다. Background/Aims: Colorectal neuroendocrine carcinoma is a rare neoplasm exhibiting fulminant progression and having poor prognosis. The purpose of this study is to verify the clinicopathologic characteristics of colorectal neuroendocrine carcinoma. Methods: From June 1997 to December 2004 at Asan Medical Center, ten patients were originally identified as colorectal neuroendocrine carcinoma on the basis of H&E and immunohistochemical staining (IHC). Carcinoid tumors were excluded in this study. Medical records of thirteen patients were reviewed retrospectively. Results: Ten patients (0.2%) with colorectal neuroendocrine tumors were identified from 4,512patients with colorectal cancer; ten neuroendocrine carcinomas and three adenocarcinomas with neuroendocrine differentiation. Their median age was 60 (41-83) years. The subjects consisted of six males and seven females. Nine tumors were located in the rectum, two in the sigmoid, and each one in the transverse colon and cecum, respectively. Nine of ten neuroendocrine carcinomas expressed synaptophysin, but chromogranin A were expressed in four. All patients were advanced at the time of diagnosis, with AJCC TNM staging: stage IIIB (n= 2), stage IIIC (n=3), and stage IV (n=8). The median survival for ten neuroendocrine carcinomas and three adenocar-cinomas with neuroendocrine differentiation were 16.4 months and 30 months, respectively. Five patients who received chemotherapy showed median survival of 32 months (stage III) and 17.5 months (stage IV), whereas other five patients without chemotherapy died with a median survival of 6.2 months. Conclusions: Colorectal neuroendocrine tumors are extremely rare showing aggressive behavior biologically, i.e fulminant early distant metastasis. Nevertheless, improved survival may be achieved by aggressive multimodality therapy. (Korean J Gastroenterol 2006;48:97-103)