The FK506 binding protein 5 (FKBP5) is a co-chaperone that regulates the activity of the glucocorticoid receptor (GR) and has been reported to mediate stress resilience. This study aimed to determine the effects of Fkbp5 deletion on acute stress-induced recognition memory impairment and hippocampal GR signaling. Wild-type and Fkbp5-knockout mice were subjected to acute uncontrollable stress induced by restraint and electrical tail shock. First, we assessed the cognitive status of mice using a novel object recognition task. Next, we measured plasma corticosterone, GR levels, and the levels of GR phosphorylation at serine 211 in the hippocampus. Wild-type mice exhibited stress-induced memory impairments, whereas Fkbp5-knockout mice did not. Plasma corticosterone and GR levels did not differ between the non-stressed wild-type and Fkbp5-knockout mice, but the levels of phosphorylated GR were lower in Fkbp5-knockout mice than in wild-type mice. Wild-type and Fkbp5-knockout mice showed increased nuclear GR levels following stress, indicating GR translocation. However, cytosolic phosphorylated GR levels were lower in the hippocampi of Fkbp5-knockout mice following stress than in those of wild-type mice. These results suggest that FKBP5 deficiency increases resilience to acute stress by altering GR signaling.

In the current investigation, the status of the septo-hippocampal cholinergic pathway and hippocampal mitogen-activated protein kinase (MAPK) signaling was examined in male Wistar rats with chronic cerebral hypoperfusion, which showed cognitive deficits based on assessment on a version of the Morris water maze. Chronic cerebral hypoperfusion was induced by bilateral common artery occlusion and maintained for 12 weeks until behavioral testing. Chronic cerebral hypoperfusion was shown to induce memory impairments and microglial activation in regions of white matter, including the fimbria of hippocampus. Choline acetyltransferase expression of the basal forebrain and expression of hippocampal MAPKs was decreased in rats with BCCAo compared to control rats. The results of this study suggest that cognitive decline induced by chronic cerebral hypoperfusion could be related to dysfunction of the basal forebrain cholinergic system and reduction of hippocampal MAPK activities.
Adult ; Animals ; Arteries ; Choline O-Acetyltransferase ; Dementia, Vascular ; Hippocampus ; Humans ; Male ; Maze Learning ; Memory ; Prosencephalon ; Protein Kinases ; Rats ; Rats, Wistar

Angiogenic factors contribute to cerebral angiogenesis following cerebral hypoperfusion, and understanding these temporal changes is essential to developing effective treatments. The present study examined temporal alterations in angiogenesis-related matrix metalloproteinase-9 (MMP-9) and angiopoietin-2 (ANG-2) expression in the hippocampus following bilateral common carotid artery occlusion (BCCAo). Male Wistar rats (12 weeks of age) were randomly assigned to sham-operated control or experimental groups, and expression levels of MMP-9 and ANG-2 were assessed after BCCAo (1 week, 4 weeks, and 8 weeks), using western blotting. Protein expression increased 1 week after BCCAo and returned to control levels at 4 and 8 weeks. In addition, immunofluorescence staining demonstrated that the MMP-9- and ANG-2-positive signals were primarily observed in the NeuN-positive neurons with very little labeling in non-neuronal cells and no labeling in endothelial cells. In addition, these cellular locations of MMP-9- and ANG-2-positive signals were not altered over time following BCCAo. Other angiogenic factors such as vascular endothelial growth factor and hypoxia-inducible factor did not differ from controls at 1 week; however, expression of both factors increased at 4 and 8 weeks in the BCCAo group compared to the control group. Our findings increase understanding of alterations in angiogenic factors during the progression of cerebral angiogenesis and are relevant to developing effective temporally based therapeutic strategies for chronic cerebral hypoperfusion-associated neurological disorders such as vascular dementia.
Angiogenesis Inducing Agents ; Angiopoietin-2* ; Animals ; Blotting, Western ; Carotid Artery, Common ; Dementia, Vascular ; Endothelial Cells ; Fluorescent Antibody Technique ; Hippocampus* ; Humans ; Male ; Matrix Metalloproteinase 9* ; Nervous System Diseases ; Neurons ; Rats* ; Rats, Wistar ; Vascular Endothelial Growth Factor A

To what extent the risks of neonatal morbidities are directly related to premature birth or to biological mechanisms of preterm birth remains uncertain. We aimed to examine the effect of exposure to amniotic fluid (AF) infection and elevated cytokine levels on the mortality and pulmonary, intestinal, and neurologic outcomes of preterm infants, and whether these associations persist after adjustment for gestational age at birth. This retrospective cohort study included 152 premature singleton infants who were born at ≤ 32 weeks. AF obtained by amniocentesis was cultured; and interleukin-6 (IL-6) and IL-8 levels in AF were determined. The primary outcome was adverse perinatal outcome defined as the presence of one or more of the followings: stillbirth, neonatal death, bronchopulmonary dysplasia, necrotizing enterocolitis, intraventricular hemorrhage, and periventricular leukomalacia. Logistic regression analysis was adjusted for gestational age at birth and other potential confounders. In bivariate analyses, elevated AF IL-6 and IL-8 levels were significantly associated with adverse perinatal outcome. These results were not changed after adjusting for potential confounders, such as low Apgar scores, mechanical ventilation, and surfactant application. However, the independent effect of elevated cytokine levels in AF disappeared when additionally adjusted for low gestational age at birth; consequently, low gestational age remained strongly associated with the risk of adverse perinatal outcome. In conclusion, elevated levels of pro-inflammatory cytokines in AF are associated with increased risk of adverse perinatal outcomes, but this risk is not independent of low gestational age at birth. Culture-proven AF infection is not associated with this risk.
Amniocentesis ; Amniotic Fluid* ; Bronchopulmonary Dysplasia ; Cohort Studies ; Cytokines ; Enterocolitis, Necrotizing ; Female ; Gestational Age ; Hemorrhage ; Humans ; Infant* ; Infant, Newborn ; Infant, Premature ; Interleukin-6 ; Interleukin-8 ; Leukomalacia, Periventricular ; Logistic Models ; Mortality* ; Parturition ; Perinatal Death ; Pregnancy* ; Premature Birth ; Respiration, Artificial ; Retrospective Studies ; Stillbirth

PURPOSE: To report on the current practices in breast magnetic resonance imaging (MRI) in Korea. MATERIALS AND METHODS: We invited the 68 members of the Korean Society of Breast Imaging who were working in hospitals with available breast MRI to participate in a survey on how they performed and interpreted breast MRI. We asked one member from each hospital to respond to the survey. A total of 22 surveys from 22 hospitals were analyzed. RESULTS: Out of 22 hospitals, 13 (59.1%) performed at least 300 breast MRI examinations per year, and 5 out of 22 (22.7%) performed > 1200 per year. Out of 31 machines, 14 (45.2%) machines were 1.5-T scanners and 17 (54.8%) were 3.0-T scanners. All hospitals did contrast-enhanced breast MRI. Full-time breast radiologists supervised the performance and interpreted breast MRI in 19 of 22 (86.4%) of hospitals. All hospitals used BI-RADS for MRI interpretation. For computer-aided detection (CAD), 13 (59.1%) hospitals sometimes or always use it and 9 (40.9%) hospitals did not use CAD. Two (9.1%) and twelve (54.5%) hospitals never and rarely interpreted breast MRI without correlating the mammography or ultrasound, respectively. The majority of respondents rarely (13/21, 61.9%) or never (5/21, 23.8%) interpreted breast MRI performed at an outside facility. Of the hospitals performing contrast-enhanced examinations, 15 of 22 (68.2%) did not perform MRI-guided interventional procedures. CONCLUSION: Breast MRI is extensively performed in Korea. The indication and practical patterns are diverse. The information from this survey would provide the basis for the development of Korean breast MRI practice guidelines.
Breast Neoplasms ; Breast* ; Diagnosis ; Korea ; Magnetic Resonance Imaging* ; Mammography ; Surveys and Questionnaires ; Ultrasonography

The receptor for advanced glycation end products (RAGE) has been reported to have a pivotal role in the pathogenesis of Alzheimer's disease (AD). This study investigated RAGE levels in the hippocampus and cortex of a triple transgenic mouse model of AD (3xTg-AD) using western blotting and immunohistochemical double-labeling to assess cellular localization. Analysis of western blots showed that there were no differences in the hippocampal and cortical RAGE levels in 10-month-old adult 3xTg-AD mice, but significant increases in RAGE expression were found in the 22- to 24-month-old aged 3xTg-AD mice compared with those of age-matched controls. RAGE-positive immunoreactivity was observed primarily in neurons of aged 3xTg-AD mice with very little labeling in non-neuronal cells, with the notable exception of RAGE presence in astrocytes in the hippocampal area CA1. In addition, RAGE signals were co-localized with the intracellular amyloid precursor protein (APP)/amyloid beta (Abeta) but not with the extracellular APP/Abeta. In aged 3xTg-AD mice, expression of human tau was observed in the hippocampal area CA1 and co-localized with RAGE signals. The increased presence of RAGE in the 3xTg-AD animal model showing critical aspects of AD neuropathology indicates that RAGE may contribute to cellular dysfunction in the AD brain.
Advanced Glycosylation End Product-Specific Receptor ; Alzheimer Disease/genetics/*metabolism ; Amyloid beta-Peptides/metabolism ; Animals ; Astrocytes/*metabolism ; CA1 Region, Hippocampal/growth & development/metabolism/pathology ; Humans ; Mice ; Mice, Transgenic ; Neurons/*metabolism ; Receptors, Immunologic/genetics/*metabolism ; tau Proteins/genetics/metabolism

OBJECTIVE: To analyze the incidence of gestational diabetes mellitus (GDM) and its clinical implication of glycosuria identified in 2nd trimester pregnancy. METHODS: This study included pregnant women who had undertaken the 50 g oral glucose tolerance test (50 g OGTT) between 24 and 28 weeks gestation and delivered at term (N=704). Blood and urine sample were collected and analyzed for glucose level, one hour after 50 g OGTT. We applied women to 100 g OGTT if their blood glucose level after 50 g OGTT were more than 140 mg/dL. We compared blood glucose level, rate of GDM, birth weight and number of macrosomia at different urine glucose levels. Urine glucose level were measured by urine dipstick test and grouped to trace, 1+, 2+, 3+, and 4+, which were corresponding to 100, 250, 500, 1,000, 2,000 mg/dL. RESULTS: Women with glycosuria after 50 g OGTT were 258/704 (36.6%). Mean blood glucose levels were 117+/-23 mg/dL, 128+/-20 mg/dL, 135+/-23 mg/dL, 132+/-17 mg/dL, 139+/-25 mg/dL, 153+/-45 mg/dL, mean birth weight 3.29+/-0.40 kg, 3.25+/-0.40 kg, 3.27+/-0.41 kg, 3.34+/-0.35 kg, 3.28+/-0.41 kg, 3.33+/-0.40 kg, and numbers of macrosomia (> or =4.0 kg) 20 (4.5%), 3 (4.8%), 1 (1.8%), 2 (4.2%), 3 (6.7%), 0 (0%) at glycosuria level of negative, trace, 1+, 2+, 3+ and 4+ respectively. Glycosuria level was correlated significantly with blood glucose level (P=0.000), but not with birth weight and macrosomia (P=0.838, 0.881). The rate of GDM was 7/55 (12.7%), 2/48 (4.7%), 7/45 (15.6%), 8/48 (16.7%) in glycosuria level of 1+, 2+, 3+, 4+ and their relationship was statistically significant (P=0.000, AUC=0.734, 95%CI 0.638-0.830). In the cut off value of glycosuria 1+ or greater, sensitivity and positive predictive value were 72.7 and 12.2%. CONCLUSION: Glycosuria correlates well with blood glucose level and GDM prevalence but not with birth weight.
Birth Weight ; Blood Glucose ; Diabetes, Gestational ; Female ; Glucose ; Glucose Tolerance Test ; Glycosuria ; Humans ; Incidence ; Pregnancy ; Pregnant Women ; Prevalence