Down-regulation of ARC contributes to vulnerability of hippocampal neurons to ischemia/hypoxia

AbstractARC is a caspase recruitment domain-containing molecule that plays an important role in the regulation of apoptosis. We examined ARC expression during neuronal cell death following ischemic injury in vivo and in vitro. After exposure to transient global ischemic conditions, the expression of ARC was substantially reduced in the CA1 region of hippocampus in a time-dependent manner with concomitant increase of TUNEL-positive cells. Quantitative analysis using Western blotting exhibited that most of ARC protein disappeared in the cultured hippocampal neurons exposed to hypoxia for 12 h and showing 60% cell viability. Forced expression of ARC in the primary cultures of hippocampal neurons or B103 neuronal cells significantly reduced hypoxia-induced cell death. Further, the C-terminal P/E rich region of ARC was effective to attenuate hypoxic insults. These results suggest that down-regulation of ARC expression in hippocampal neurons may contribute to neuronal death induced by ischemia/hypoxia

Prediction of Alzheimer's disease pathophysiology based on cortical thickness patterns

AbstractIntroductionRecent studies have shown that pathologically defined subtypes of Alzheimer's disease (AD) represent distinctive atrophy patterns and clinical characteristics. We investigated whether a cortical thickness–based clustering method can reflect such findings.MethodsA total of 77 AD subjects from the Alzheimer's Disease Neuroimaging Initiative 2 data set who underwent 3-T magnetic resonance imaging, [18F]-fluorodeoxyglucose-positron emission tomography (PET), [18F]-Florbetapir PET, and cerebrospinal fluid (CSF) tests were enrolled. After clustering based on cortical thickness, diverse imaging and biofluid biomarkers were compared between these groups.ResultsThree cortical thinning patterns were noted: medial temporal (MT; 19.5%), diffuse (55.8%), and parietal dominant (P; 24.7%) atrophy subtypes. The P subtype was the youngest and represented more glucose hypometabolism in the parietal and occipital cortices and marked amyloid-beta accumulation in most brain regions. The MT subtype revealed more glucose hypometabolism in the left hippocampus and bilateral frontal cortices and less performance in memory tests. CSF test results did not differ between the groups.DiscussionCortical thickness patterns can reflect pathophysiological and clinical changes in AD

Association between Alcohol Intake and Abdominal Obesity among the Korean Population

OBJECTIVES: Although abdominal obesity has been reported to be highly related with alcohol intake, the results are still inconclusive. Therefore, this study was conducted to explore the association between alcohol and abdominal obesity among the Korean population. METHODS: This study included 8,603 participants (men: 5,195, women: 3,408) aged 30 to 87 who visited the health promotion centers in Seoul for routine health examinations from April, 2006 to June, 2007. Abdominal obesity was defined as WC ≥90 cm for men and ≥85 cm for women in accordance with the Korean Society for the Study of Obesity. For ever drinkers, total alcohol consumption in grams was classified into four groups (group 1, non-drinkers; group 2, 1-10 g of alcohol per day; group 3, 11-20 g of alcohol per day; and group 4, over 20 g of alcohol per day). RESULTS: The mean age of the study population was 45.4 yr old (men) and 45.3 yr (women). The average waist circumference was 85.3 cm in men and 75.3 cm in women. A high alcohol intake was associated with high waist circumference in both genders. In multivariate analysis, the group of men and women drinkers consuming >20 g in a day had a large waist circumference compared with men and women non-drinkers. CONCLUSION: This study showed that a high alcohol intake was related to high waist circumference. Such association remained independently even after adjustment for smoking, which is strongly related to abdominal obesity.ope

iPSC Modeling of Presenilin1 Mutation in Alzheimer's Disease with Cerebellar Ataxia.

Disease modeling of Alzheimer's disease (AD) has been hampered by the lack of suitable cellular models while animal models are mainly based on the overexpression of AD-related genes which often results in an overemphasis of certain pathways and is also confounded by aging. In this study, we therefore developed and used induced pluripotent stem cell (iPSC) lines from a middle-aged AD patient with a known presenilin 1 (PSEN1) mutation (Glu120Lys; PS1-E120K) and as a control, an elderly normal subject. Using this approach, we demonstrated that the extracellular accumulation of Aβ was dramatically increased in PS1-E120K iPSC-derived neurons compared with the control iPSC line. PS1-E120K iPSC-derived neurons also exhibited high levels of phosphorylated tau, as well as mitochondrial abnormalities and defective autophagy. Given that the effect of aging is lost with iPSC generation, these abnormal cellular features are therefore indicative of PSEN1-associated AD pathogenesis rather than primary changes associated with aging. Taken together, this iPSC-based approach of AD modeling can now be used to better understand AD pathogenesis as well as a tool for drug discovery.This work was supported by the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (HI14C2746) and a grant (2016-0588) from the Asan Institute for Life Sciences

OCT-guided Hyaloid Release for Vitreomacular Traction Syndrome

PURPOSE: To evaluate the usefulness of OCT retinal mapping in determining the configuration of a vitreomacular adhesion and selecting a meridian for entry into the subhyaloid space in patients with vitreomacular traction syndrome. METHODS: Six consecutive patients (6 eyes) with vitreomacular traction syndrome underwent vitrectomy with peeling of posterior hyaloid. Ocular coherence tomography (OCT) retinal mapping was performed preoperatively. Access to the subhyaloid space was made by creating an opening with a 25 gauge needle at a location where the detached posterior hyaloid membrane was farthest from the retinal surface. The location was selected based on six preoperative meridional OCT scans. The posterior hyaloid was then gently peeled off in a circular fashion around the fovea with a micropick. Visual acuity and foveal thicknesses were measured before the operation and 3 months afterwards. RESULTS: After the operation, visual acuity improved and central macular thicknesses were reduced significantly in all six patients. The best corrected visual acuity improved from 0.4 to 0.75 with a mean increase by 3.5 lines on a Snellen chart 3 months after the operation. The mean foveal thickness was reduced from 406 micrometer to 241 micrometer. The restoration of foveal pit was observed in five patients. Neither intraoperative nor postoperative complications were observed during the follow up period. CONCLUSIONS: An OCT retinal mapping program is a valuable diagnostic tool in understanding the configuration of vitreomacular adhesion and planning the surgical approach for operating on vitreomacular traction syndromeope

Genetic Analysis of Three Korean Patients with Clinical Features of Ehlers-Danlos Syndrome Type IV

Ehlers-Danlos syndrome (EDS) is a hereditary disorder of the connective tissue. EDS type IV (EDS IV), the vascular type of the disease, is characterized by easy bruising, thin skin with visible veins, and spontaneous rupture of the large arteries, uterus, or bowel. EDS IV is caused by mutations in the gene for type III procollagen (COL3A1). However, recent studies suggest that the causative mutation of EDS IV is not homogeneous. We report our experience with three patients presenting with clinical features of type IV EDS. A 48-yr-old woman presented with acute aortic dissection (patient 1) and 36-yr-old and 21-yr-old women presented with carotid-cavernous fistula (patients 2 and 3, respectively). All three patients bruised easily. Two patients (patients 1 and 3) had thin transparent skin with visible veins. Genetic analysis of COL3A1 revealed a Gly732Val (c.2195G>T) mutation in patient 1 and a duplication of 15 base pairs (c.3221_3235dup) which resulted in an interposition of five amino acids (p.Gly1074_Pro1078dup) in patient 2. However, no mutations were observed in COL3A1 or transforming growth factor β receptors 1 and 2 in patients 3, which might be either due to a deletion of single or multiple exons in the COL3A1 gene or due to a genetic heterogeneity. This is the first report of genetically confirmed cases of EDS IV in Korea

Coffee Consumption and Bone Mineral Density in Korean Premenopausal Women

Background: Although Asian people are known to have lower bone mass than that of Caucasians, little is known about coffee-associated bone health in Asian. This study aimed to assess the relationship between coffee consumption and bone mineral density (BMD) in Korean premenopausal women.Methods: Data were obtained from the Fourth Korea National Health and Nutrition Examination Survey 2008?2009. The study population consisted of 1,761 Korean premenopausal women (mean age 36 years) who were measured for lumbar spine and femoral neck BMD and who completed a standardized questionnaire about coffee intake frequency. We excluded the participants who took hormone replacement therapy or medication for osteoporosis. The cross-sectional relationship between coffee consumption and impaired bone health (osteopenia or osteoporosis) was investigated by bone densitometry.Results: Coffee consumption showed no significant association with BMD of either femoral neck or lumbar spine, independent of other factors. The adjusted odds ratios for BMD for those who consumed once in a day, twice a day and three times a day were 0.94 (0.70?1.26), 0.93 (0.67?1.28), and 1.02 (0.69?1.50), respectively (P for trend = 0.927).Conclusion: This study does not support the idea that coffee is a risk factor for impaired bone health in Korean premenopausal women.OAIID:oai:osos.snu.ac.kr:snu2014-01/102/0000052039/9SEQ:9PERF_CD:SNU2014-01EVAL_ITEM_CD:102USER_ID:0000052039ADJUST_YN:YEMP_ID:A079543DEPT_CD:806CITE_RATE:0FILENAME:coffee consumption and bone mineral density in korean premenopausal women.pdfDEPT_NM:의과학과SCOPUS_YN:NCONFIRM: