Comparison of Proliferative Activity in Each Histological Subtypes of Benign and Atypical Intracranial Meningiomas by PCNA and Ki-67 Immunolabeling

최승진,장은덕,권성오,계대곤,박춘근,이상원,강준기,Choi, Seung Jin,Chang, Eun Deok,Kwon, Seung Oh,Kye, Dae Kon,Park, Choon Keun,Lee, Sang Won,Kang, Joon Ki The Korean Neurosurgical Society 2000 Journal of Korean neurosurgical society Vol.29 No.9

목 적 : 양성 뇌수막종에 비하여 이형성 및 악성 뇌수막종이 나쁜 임상적인 예후 및 양상을 보이는 것은 잘 알려져 있으나, 양성 뇌수막종에 있어서 각각의 병리조직학적 아형에 따른 생물학적 양상의 차이에 대해서는 잘 알려지지 않거나 일부 논란이 되고있다. 본 연구에서는 이형성 뇌수막종 및 양성 뇌수막종의 각각의 병리조직학적 아형에 따른 증식능의 차이여부를 알아보고자 PCNA와 Ki-67표지지수를 분석하였다. 방 법 : 본원에서 뇌수막종으로 수술을 시행하여 얻은, 재발을 보여 재수술을 시행한 2례를 포함하여, 파라핀에 포매시킨 27개의 조직을 대상으로 병리학적인 증식능을 분석하기 위해, PCNA에 대한 단일항체 및 MIB-1 단일항체를 이용한 면역조직화학적 염색을 시행하였다. 조직학적 분류상 meningothelial type이 8례, transitional type이 9례, fibroblastic type이 5례였으며, 이형성 수막종이 5례였다. 결 과 : PCNA표지지수의 평균값은 양성 수막종에서 meningothelial type이 $4.82{\pm}5.10%$, transitional type이 $9.01{\pm}4.25%$, fibroblastic type이 $5.66{\pm}5.32%$를 보였으나 이형성 수막종에서는 $27.62{\pm}19.67%$의 높은 지수를 나타냈고, Ki-67 표지지수의 평균값은 양성 수막종의 아형에서 각각 $0.43{\pm}0.85%$, $0.44{\pm}1.08%$, $0.24{\pm}0.18%$를 보이고, 역시 이형성 수막종에서는 $0.84{\pm}0.59%$의 높은 지수를 보였다. 즉, 양성 수막종에서 각각의 아형에 따른 PCNA 및 Ki-67 표지지수는 통계학적으로 의미있는 차이는 없었으나(p>0.05), 이형성 수막종에서는 의미있는 높은 표지지수를 보여(p<0.05) 양성 수막종에서 보다 높은 증식능을 보임을 알 수 있었다. 결 론 : PCNA 및 Ki-67 표지지수를 이용한 증식능의 비교결과, 양성 뇌수막종에서는 각각의 아형에 따른 생물학적 양상이나 예후는 차이가 없을것으로 생각되나, 이형성 수막종에서는 높은 증식능을 보여 이에 대한 예후를 예상할 수 있을것으로 생각되며, 또한 이러한 표지지수가 병리조직학적으로 양성과 이형성의 감별에 많은 도움이 될것으로 사료된다. Objective : The clinical prognosis and biological behavior of atypical and especially malignant meningiomas are well known to be worse than benign meningioma, but the degree of biological aggressiveness in each classical subtypes of benign meningioma is controversy. This study was performed to see whether there is a difference in the proliferative activity between each different histological subtypes of benign meningioma as well as atypical meningioma. Methods : Paraffin-embedded surgical specimens of 27 meningiomas, including two recurrent tumors, were studied to evaluate proliferative activity by immunohistochemical method with monoclonal antibodies to proliferating cell nuclear antigen(PCNA) and MIB-1. The specimens consisted of 8 cases of meningothelial, 9 cases of transitional, 5 cases of fibroblastic subtypes and 5 cases of atypical meningiomas. Results : Mean PCNA labeling indices of meningothelial, transitional and fibroblastic meningiomas were $4.82{\pm}5.10%$, $9.01{\pm}4.25%$ and $5.66{\pm}5.32%$, but that of atypical meningiomas was $27.62{\pm}19.67%$, noting a higher value compared to all three subtypes of benign meningiomas. Mean Ki-67 labeling indices of the above 3 subtypes were $0.43{\pm}0.85%$, $0.44{\pm}1.08%$ and $0.24{\pm}0.18%$, and that of atypical meningiomas was also revealed to be of higher value ($0.84{\pm}0.59%$). PCNA and Ki-67 labeling indices were not statistically different between histological subtypes of benign meningioma(p>0.05), but the differences of both immunolabeling between benign and atypical meningiomas were statistically significant(p<0.05). Conclusion : Immunolabeling of PCNA and Ki-67 in intracranial meningiomas reveals no prognostic difference between meningothelial, transitional and fibroblastic subtypes in classical benign meningiomas by measuring expression of PCNA and Ki-67, but it seems to be helpful in differentiating benign and atypical meningioma, later showing more proliferative activity and biological aggressiveness.

Differential Manifestation of Ocular Phenotypes in TALEN-mediated p19arf Knockout FVB/N and C57BL/6J mouse lines

Jin‑Sung Park,Joo‑Il Kim,Hyun‑Jin Lim,Soo‑Kyung Ryu,Euna Kwon,Kang‑Min Han,Ki‑Taek Nam,Han‑Woong Lee,Byeong‑Cheol Kang 한국유전학회 2020 Genes & Genomics Vol.42 No.9

Background p19arf, primarily known as a tumor suppressor, has also been reported to play an essential role in normal development of mouse eyes. Consistently, lack of p19arf has been associated with ocular defects, but the mixed background of the knockout (KO) mouse strain used raised a concern on the accuracy of the phenotypes observed in association with the targeted gene due to genetic heterogeneity. Object We carried out a study to investigate into the efect of genetic background on the manifestation of p19arf KO associated phenotypes. Methods We characterized the phenotypes of novel p19arf KO mouse lines generated in FVB/N and C57BL/6J using a transcription activator-like efector nuclease (TALEN) system in comparison to the reported phenotypes of three other p19arf-defcient mouse lines generated using homologous recombination. Results Ninety-fve percent of FVB/N-p19arf KO mice showed ocular opacity from week 4 after birth which worsened rapidly until week 6, while such abnormality was absent in C57BL/6J-p19arf KO mice up to the age of 26 weeks. Histopathological analysis revealed retrolental masses and dysplasia in the retinal layer in FVB/N-p19arf KO mice from week 4. Besides these, both strains developed normally from birth to week 26 without increased tumorigenesis except for a subcutaneous tumor found in a C57BL/6J-p19arf KO mouse. Conclusion Our fndings demonstrated surprisingly variable manifestation of p19arf-linked phenotypes between FVB/N and C57BL/6J mice, and furthermore between our mouse lines and the established lines, indicating a critical impact of genetic background on functional study of genes using gene targeting strategies in mice.

2003년 국내 중증급성호흡기증후군 진료 현황 및 문제점 분석

이진수,김은실,정문현,백제중,정선화,안주희,최영화,이선희,고철우,김성범,김민자,박승철,기현균,송재훈,최상호,김양수,이상오,조용균,박영훈,정숙인,김연숙,이흥범,손창희,장성희,정희진,김우주 대한감염학회 2004 감염과 화학요법 Vol.36 No.3

목적 : 2002년 말 중국에서 SARS가 발생한 이후 국내에서도 2003년 10월까지 총 3명의 추정환자, 17명의 의심환자가 보고되었다. 향후 추가적인 SARS의 유행이 우려되는 상황에서, 그간의 SARS 환자 진료에 있어서의 실질적인 준비사항, 진료 현황 등에 대한 조사를 통해 문제점을 파악하여, 향후 더 나은 대비가 될 수 있도록 개선점을 제시하고자 하였다. 재료 및 방법 : SARS로 의심되는 환자를 진료 경험이 있는 병원의료진을 대상으로 2003년 10월에 설문조사를 실시하였다. 설문에는 SARS 환자 진료 시의 실질적인 조치, 진료 현황, 병실, 응급실 및 외래에서의 격리 시설과 준비사항, 보건당국의 관리와 지원에 관한 사항을 포함하였다. 결과 : 대상이 되는 22개 병원 중 17개(17/22, 77.2%) 병원이 설문에 응하였다. SARS 환자를 위한 격리실은 응급실, 외래, 일반병실 및 중환자실에서 각각 9개(9/17, 52.9%), 5개(5/17, 29.4%), 15개(15/16, 93.7%), 4개(4/16, 25%) 병원에서 음압처리가 되어있지 않은 일인실 혹은 다인실이 사용되었고, 1개(1/16, 6.3%) 병원에서만 일반병실에서 음압격리실이 운영되었다. 입원환자의 진찰 시 개인보호구의 착용은 거의 모든 의료기관에서 이루어졌다. 보건당국에서 SARS지정병원의 시설 등을 사전에 확인한 곳은 1곳(1/12, 8.3%)이였고, 14개 병원(14/15, 93.3%)에서는 보건당국에 의뢰한 검사결과를 통하 받지 못하였다. 결론 : 의료기관에서 SARS 환자용 격리실뿐만 아니라 기존의 격리실 설비 등이 미흡하였으며, 특히 중환자실 및 외래의 준비가 더욱 부족하였다. 보건당국의 의료기관에 대한 종합적인 지원이 부족하였고, 병원과의 원활한 연계가 잘 이루어지지 않았다. SARS 만이 아닌 격리를 필요로 하는 질환의 적절한 진료를 위해 향후 병원 시설의 정비와 정부차원에서의 보다 구체적이고 실질적인 대책마련이 필요하다. Background : There was an worldwide outbreak of the Severe Acute Respiratory Syndrome (SARS) originated from China in late 2002. During that period three cases of suspected SARS and 17 cases of probable SARS were reported in Korea. With the concerns about the reemergence of SARS-coV transmission, it is important to be prepared for any possibility. So, this study is aimed to analysis the past measures in managing SARS and propose the amendatory plans to improve the preparedness. Materials & Methods : Questionnaires were collected among clinicians with any experience in managing the probable or suspected SARS cases in Oct. 2003. 17 out of 22 hospitals responded to the questionnaire. The contents in the questionnaire were practical activities, personal equipments, response plans, isolation facilities in emergency centers, outpatient clinics, general wards and intensive care units, and relationship with the public health department. Results : The dedicated isolation rooms in emergency centers, outpatient clinics, general wards, and intensive care units were prepared in 9 (9/17, 52.9%), 5 (5/17, 29.4%), 15 (15/16, 93.7%), and 4 (4/16, 25.0%) hospitals, respectively. Except for one hospital that newly made negative pressure room for SARS, single or multi-bed rooms without airborne infection control were used in all the other hospitals. The personal precaution principles were kept quite well in general wards. Before the designation of SARS hospital by the public health department prior evalution to see if the hospital was suitable for managing SARS was conducted in only 1 (1/12, 8.3%) hospital. The results of laboratory diagnosis were reported back in 1 (1/15, 6.6%) hospital. Conclusions : The isolation facilities which can control airborne infection were almost deficient not only for SARS but also for other respiratory transmissible diseases. For the infection control of transmissible diseases including SARS, more investment is needed on medical facilities and comprehensive support from the public health department required.

초음파 영상 데이터를 활용한 내장기 추나요법 시술 부위 탐색 연구

이상진 ( Sang-jin Lee ),기성훈 ( Sung-hoon Ki ),고동균 ( Dong-kyun Koh ),이상훈 ( Sang-hun Lee ),임형호 ( Hyoung-ho Lim ),송윤경 ( Yun-kyung Song ) 한방재활의학과학회 2022 한방재활의학과학회지 Vol.32 No.2

Objectives This study was conducted to confirm anatomical information near the treatment areas of visceral chuna manual therapy and to secure stability and effectiveness during the treatment. Methods For 50 healthy adult men and women, a total of 13 ultrasound images were taken of the 7 treatment areas which are the representative treatment areas of visceral Chuna manual therapy. Results The treatment area of the bottom of the liver can be palpated around the right side ST19 and CV14. The treatment area of the gallbladder and the common bile duct can be palpated around the right side SP16 and ST20. The treatment area of the cardia and the pylorus can be palpated around the left side KI21, right side ST20, ST21, KI19, KI20, CV12, and CV13. The origin point of the mesentery root can be moved to the left and lower left from CV12 and can be palpated. The treatment area of the ileocecal valve and the cecum can be palpated around the right side SP14. The treatment area for the colic flexure can be palpated around the both side LR13. The treatment support point for the kidneys can be palpated around both side BL51. Conclusions It is thought that if the ultrasound image data from the meridians around the treatment site is used as an auxiliary, it will be more effective in terms of safety and effectiveness during the treatment of visceral Chuna manual therapy. (J Korean Med Rehabil 2022;32(2):139-154)

Expression Profiles of Retinoblastoma Protein and p27Kip1 According to HER2 Amplification Status in Primary Breast Cancer

신재호,Sung-Jin Park,Hyun-Jin Cho,Geumhee Gwak,Byung-Noe Bae,Ki Whan Kim,Hong-Yong Kim2,Kyeongmee Park,Sehwan Han 한국유방암학회 2009 Journal of breast cancer Vol.12 No.1

Purpose: Human epidermal growth factor receptor-2 (HER-2)/neu amplification affects the cell proliferation through the modulation of multiple G1 cell cycle regulators in breast tumor cells. We performed this study to investigate whether retinoblastoma protein (pRB) and p27Kip1 were differently expressed according to the HER2 amplification status in human breast cancer. Methods: HER2 amplification was assayed by fluorescence in situ hybridization and the expression of cell cycle regulators were assayed by immunohistochemistry on 153 consecutive invasive breast cancers. The proliferative activity of breast cancer was analyzed according to the HER2 amplification and cell cycle protein expression status. Results: HER2 amplification was observed in 39 (25.5%) of 153 breast cancers. In the HER2 amplified breast cancers, the pRB expression was significantly increased (p=0.011) whereas there was no significant relationship between HER2 amplification and p27Kip1 expression. There was an inverse correlation between pRB expression and Ki-67 labeling index in the HER2 amplified breast cancers (p=0.036). In contrast, Ki67 labeling index was significantly decreased as p27Kip1 expression increased in HER2 non-amplified breast cancers (p=0.028). In HER2 non-amplified breast cancers, we could not observe any association between the pRB expression and Ki67 labeling index. Conclusion: The proliferation of the breast cancers was associated with pRB expression in HER2 amplified tumors whereas it was associated with p27Kip1 expression in HER2 non-amplified tumors. The results of the current study indicate that the cell proliferative activity of the breast cancer is under different growth signal pathways according to HER2 amplification status.

녹동균 세포외막 단백질 백신 CFC-1-101의 안정성 및 면역원성 검토 : 임상 제 Ⅰ/Ⅱa상 시험

장인진,김익상,유경상,임동석,김형기,신상구,장우현,박완제,이나경,정상보,안동호,조양제,안보영,이윤하,김영지,남성우,김현수 대한감염학회 1998 감염 Vol.30 No.3

목적 : 제일제당에서는 녹농균의 세포외막 단밸질을 유효성분으로 하는 백신인 CFC-101을 개발하였으며, 동물시험에서 이 백신의 안전성과 유효성을 입증하였다. 본 연구에서는 이 녹농균 백신의 인체에 대한 안전성과 면역원성을 평가하는 동시에 인체 접종시의 최적 투여 용량을 결정하기 위하여 제 I/Ⅱa상 임상시험을 수행하였다. 방법 : 건강한 성인 남자를 피험자로 선별하여 각 용량군에 백신투여자 6명, 위약투여자 2명을 배정하였다. 백신 투여군은 0.25mg, 0.5mg 또는 1.0mg 용량의 녹농균 백신을 7일 간격으로 3회에 걸쳐 근육주사 하였으며, 위약 투여군에게는 세포외막 단백질을 제외한 동일한 성분을 투여하였다. 백신접종 후 국소적 또는 전신적인 반응의 발생여부를 관찰하고, 혈액시료를 체취하여 백신의 역가와 유효성을 검정하였다. 결과 : 녹농균 백신 CFC-101은 모든 접종자에서 양호한 내약성을 보였다. 또한 0.5mg 과 1.0mg 백신 투여군에서는 100%의 항체양전율을 나타내었다. 생성된 항체는 녹농균 세포외막단백질에 특이성을 보였고, 녹농균 감염에 대해 방어효능이 있었다. 결론 : 이와같은 결과로부터 이 녹농균 백신은 인체에 안전하게 투여할 수 있으며, 높은 항체 생성능으로 감염방어 효능을 보이고 0.5mg과 1.0mg이 최적용량인 것으로 판단되었다. Background : We developed a Pseudomonas aeruginosa outer membrane protein(OMP) vaccine CFC-101, and the prophylactic efficacy of which has been demonstrated in animal models. In order to evaluate the safety and immunogenicity of the P. aeruginosa vaccine, we carried out a phase I/Ⅱa clinical trial in healthy male volunteers. Methods : Groups of eight volunteers, including two placebo subjects, were vaccinated intramuscularly with three doses of 0.25, 0.5 or 1.0 mg of the vaccine at one week intervals. Sings of systemic and local reactions observed after vaccination were recorded for each vaccinee for 5 days. Physical examinations were performed on days 0, 1, 7, 8, 14, 15, 21, and 42, and clinical laboratory tests were done on days 0, 3, and 21. Blood samples for assay of serum antibody levels were obtained up to 42 days after the first vaccination. Results : The vaccine was generally well tolerated by all vaccinees, showing no significant side effects. In the three dosage groups, all vaccinees, except one receiving the 0.25 mg dose, showed significant elevation in serum IgG antibody titers against the vaccine proteins, indicating 100% seroconversion in 0.5 and 1.0 mg groups. The human antibodies induced by the vaccine were specific for P. aeruginosa OMPs, as confirmed by western blot analysis and immunoprecipitation assays. The capacity of the human antisera to enhance opsonophagocytic killing activity by polymorphonuclear leukocytes and to confer protection against P. aeruginosa infections indicates that the antibodies elicited by the vaccine have protective efficacy. Conclusion : We conclude that the P. aeruginosa OMP vaccine is safe and effective for human use and its optimal dose to be 0.5 or 1.0 mg.

소화불량(消化不良)과 과심상(過心傷)의 상관성(相關性)에 대(對)한 고찰(考察) -스트레스, 기울(氣鬱), 비병증(脾病證)의 평가(評價)를 통(通)해-

김진성,윤상협,류봉하,류기원,이상욱,Kim, Jin-Sung,Yoon, Sang-Hyub,Ryu, Bong-Ha,Ryu, Ki-Won,Lee, Sang-Wook 대한한방내과학회 2004 大韓韓方內科學會誌 Vol.25 No.4

Background & Object : Dyspepsia for which no organic causes are disclosed is referred to as functional dyspepsia. Functional dyspepsia is here studied in connection with a biopsychosocial model. From the aspect of individual response to external environment, in connection with stress response, functional dyspepsia is studied by both the psychology department and the internal medicine departments. The disease is taken as approachable from the aspect of internal injury due to seven emotions and stress as differentiated by Oriental medicine. Materials and Methods : Targeted at 223 patients underwent medical checks and endoscopy at Kangnam Korean Hospital, Kyunghee University. They agreed to join this clinical experiment. Stress response inventory, GARS (global assessment of recent stress scale), GSRS (gastrointestinal symptom rating scale), diagnostic scores for Ki-depression, and Spleen Disease Differentiation of Syndromes were all measured and evaluated. The test group was comprised of functional dyspepsia patients. The control group was comprised of nonsymptomatic chronic gastritis patients who were found to suffer from chronical gastritis in endoscopy and thus could be diagnosed with functional dyspepsia if symptoms would arise, but did not complain of subjective symptoms. Results showed these corelations: Functional dyspepsia patients were found to have more serious Ki-depression compared to nonsymptomatic chronic gastritis patients. The more serious Ki-depression the more serious the dyspepsia symptoms. The higher the stress response inventory the more serious the dyspepsia. Deficiency of spleen Eum, and Deficiency and Sinking of spleen Gi were found to coincide with serious Ki-depression.

서울의 PPNG 발생 빈도(1991-1992)

김재홍,윤기범,박평원,김영진,전경민,김영태,김중환,곽호,구상완,송민석,유옥,지혜구,김동원,문상은,박영립,정승호,성범진,성순제,엄주용,황정열,이기홍,이주협,전태진 대한화학요법학회 1994 대한화학요법학회지 Vol.12 No.1

The prevalence of PPNG among pretreated gonorrhea cases isolated at the STD clinic of Choong-Ku Public Health Center in Seoul has been studied and reported annually since 1981. In 1991, 123 strains of N.gonorrhoeae were isolated, among which 58(47.1%) were PPNG. In 1992, 98 starains of N.gonorrhoeae were isolated, among which 51(52.0%) were PPNG. In all, 109(49.3%) strains were found to be PPNG among 221 strains isolated between 1991-1992. The prevalence of PPNG in Seoul showed increased tendency till 1989, thereafter, it has been stationary or slightly decreasing.

광주광역시 전문계 고등학교 특성화 및 종합발전방안

나승일,정철영,김진모,안강현,한홍진,김기용,민상기,장현진 한국농업교육학회 2008 농업교육과 인적자원개발 Vol.40 No.1

이 연구의 목적은 광주광역시 전문계 고등학교의 특성화 및 종합발전방안을 수립하는데 있다. 이 연구는 ① 전문계 고등학교 관련 선행연구 분석,② 인력육성 및 특성화 방향을 설정하기 위하여 광주광역시,전라남도,우리나라의 산업여건 분석,③ 광주광역시 전문계 고등학교에 대해 Malcolm Baldrige 평가모형에 의한 진단평가와 SWOT 및 활용전략 분석, ④ 광주광역시 전문계 고등학교의 개편 요구 분석,⑤ 광주광역시 전문계 고등학교의 특성화 및 종합발전방안 설정 등의 과정을 통해 수행되었다. 이 연구의 결과는 다음과 같다. 첫째,비전은 광주광역시 전문계고 특성화와 발전 역량 구축을 통한 산업체 요구에 부합하는 우수 인력 양성이며,이를 위한 전략은 특성화 체제구축,학교교육 혁신,인적 자원 혁신,학교경영 혁신,인프라 구축으로 설정하는 것이 필요하다. 둘째, 특성화 체제 구축은 특성화 체제 개편,교육과정 중심 특성화,학과 재배치 통합형 고교 도입,특성화고 신설을 통해 추진할 수 있 는데 특히,교육과정 중심 특성화가 적극 도입되어야 한다. 셋째,학교교육 혁신은 교육과정 개편,교수 학습 개선,진로지도 개선,시설 및 기자재 개선을 통해 추진할 수 있다. 넷째,인적자원 혁신은 학교 관리자 역량 강화,교원 역량 강화,학생 역량 강화를 통해 추진할 수 있다. 다섯째,학교경영 혁신은 경영 리더십 제고,경영 성과관리 강화,학교 재정 혁신을 통해 추진할 수 있다. 여섯째,인프라 구축을 위해 지자체,대학,산업체,지역주민과 연계 강화를 통해 추진할 수 있다. 일곱째,13개 전문계 고둥학교의 여건 및 특성에 적합한 단위학교별 특성화 및 종합발전방안을 수립하였다. The purpose of this study was to suggest strategies to specialize and develop vocational high schools in Gwangju Metropolitan City. The study was orderly performed as follows: (1) reviewing literature about vocational high school, (2) analyzing the condition of industries, (3) diagnosing the vocational high school through Malcolm Baldrige model, (4) analyzing the SWOT and application strategies, (5) analyzing the needs of reform, and (6) establishing the strategies for the specialization and development of Vocational High Schools in Gwangju Metropolitan City. The major findings of this study were as the following: First, the vision was to bring up excellent human resources to corresponds industrial needs through specialization and development of vocational high schools in Gwangju Metropolitan City. Five strategies to achieve it were creating the specialization system, innovating the school education, human resources, and the school management, and building the infrastructure. Second, creating the specialization system can be performed through five tasks which were restructuring the specialization system, creating curriculum-based specialization, trading departments in inter-schools, introducing an integrated high school, and building a new specialized high school. Especially curriculum based specialization needs to be accepted. Third, innovating the school education can be performed through four tasks which were reorganizing the curriculum, improving the teaching and learning, improving the career guidance, and improving the facilities and equipments. Fourth, innovating human resources can be performed through three tasks which were enhancing each competencies of a school manager, a teacher, and a student. Fifth, innovating the school management can be performed through three tasks which were improving the management leadership, developing the performance management, and innovating the school finance. Sixth, building the infrastructure can be performed through four tasks which were enhancing the relationships with a local government, colleges, industries, and local residents. Seventh, individual strategies for the specialization and development of thirteen vocational high schools were also developed by corresponding to their conditions and characteristics.

Effects of pyridoxine on a high‐fat diet‐induced reduction of cell proliferation and neuroblast differentiation depend on cyclic adenosine monophosphate response element binding protein in the mouse dentate gyrus

Yoo, Dae Young,Kim, Woosuk,Yoo, Ki‐,Yeon,Nam, Sung Min,Chung, Jin Young,Yoon, Yeo Sung,Won, Moo‐,Ho,Hwang, In Koo Wiley Subscription Services, Inc., A Wiley Company 2012 JOURNAL OF NEUROSCIENCE RESEARCH - Vol.90 No.8

<P><B>Abstract</B></P><P>In this study, we challenged pyridoxine to mice fed a high‐fat diet (HFD) and investigated the effects of pyridoxine on HFD‐induced phenotypes such as blood glucose, reduction of cell proliferation and neuroblast differentiation in the dentate gyrus using Ki67 and doublecortin (DCX), respectively. Mice were fed a commercially available low‐fat diet (LFD) as control diet or HFD (60% fat) for 8 weeks. After 5 weeks of LFD or HFD treatment, 350 mg/kg pyridoxine was administered for 3 weeks. The administration of pyridoxine significantly decreased body weight in the HFD‐treated group. In addition, there were no significant differences in hepatic histology and pancreatic insulin‐immunoreactive (‐ir) and glucagon‐ir cells of the HFD‐treated group after pyridoxine treatment. In the HFD‐fed group, Ki67‐positive nuclei and DCX‐ir neuroblasts were significantly decreased in the dentate gyrus compared with those in the LFD‐fed mice. However, the administration of pyridoxine significantly increased Ki67‐positive nuclei and DCX‐ir neuroblasts in the dentate gyrus in both LFD‐ and HFD‐fed mice. In addition, the administration of pyridoxine significantly increased the protein levels of glutamic acid decarboxylase 67 (GAD67) and brain‐derived neurotrophic factor (BDNF) and the immunoreactivity of phosphorylated cyclic AMP response element binding protein (pCREB) compared with the vehicle‐treated LFD‐ and HFD‐fed mice. In contrast, the administration of pyridoxine significantly decreased HFD‐induced malondialdehyde (MDA) levels in the hippocampus. These results showed that pyridoxine supplement reduced the HFD‐induced reduction of cell proliferation and neuroblast differentiation in the dentate gyrus via controlling the levels of GAD67, pCREB, BDNF, and MDA. © 2012 Wiley Periodicals, Inc.</P>