Pancreatic islet transplantation can correct the abnormal glucose metabolism of Type 1 diabetes. Although immunosuppressants greatly reduce the acute rejection rate in transplant patients, the long-term side effects can be debilitating. Therefore, researchers are seeking to develop new immunosuppressive regimens that induce maximal levels of immunosuppression with minor side effects. Rosmarinic acid (Ros A) is a secondary metabolite of certain herbs and has multiple biological activities, including anti-inflammatory effects. Here, we have investigated whether treatment of mice with a combination of Ros A and anti-CD154 monoclonal antibody (MR1) improves islet allograft survival in a murine model. After transplantation, the mice were treated with either Ros A, MR1, or both (the "double" treatment). Allograft survival was prolonged in the double-treated animals compared to animals that received only Ros A or MR1. As is the case with the single-treated animals at 15 days after transplantation, the double-treated recipients did not display a significant decrease in the expression of cytokines or the population of activated T cells. Infiltrating CD3+ T cells were reduced in the MR1- or double therapy relative to control or RosA group. However, at the same time point, double-treated graft showed fewer apoptotic cells and increased expression of insulin and glucagons, compared to the single-treatment groups. Furthermore, long-term (> 150 days) allografts that were received with double therapy exhibited larger islet clusters and contained more insulin- and glucagon-positive cells, relative to the MR1-treated grafts. In conclusion, treatment with both Ros A and MR1 has a synergistic effect in murine islet allotransplantation.
apoptosis; CD40 ligand; graft survival; immunosuppressive agents; islets of Langerhans transplantation; rosmarinic acid
For tissue diagnosis of suspected pancreatic cancer, endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is the procedure of choice with high safety and accuracy profiles. However, about 10% of cytologic findings of EUS-FNA are inconclusive. In that situation, careful observation, surgical exploration, or alternative diagnostic tools such as bile duct brushing with endoscopic retrograde cholangiopancreatography or computed tomography-guided biopsy can be considered. However, some concerns and/or risks of these options render repeat EUS-FNA a reasonable choice. Repeated EUS-FNA may impose substantial clinical impact with low risk.
Endosonography; Endoscopic ultrasound-guided fine needle aspiration; Pancreatic neoplasms
Topics related with endoscopic ultrasound (EUS) made up considerable portion among many invited lectures presented in International Digestive Endoscopy Network 2012 meeting. While the scientific programs were divided into the fields of upper gastrointestinal (UGI), lower gastrointestinal, and pancreato-biliary (PB) categories, UGI and PB parts mainly dealt with EUS related issues. EUS diagnosis in subepithelial lesions, estimation of the invasion depth of early gastrointestinal cancers with EUS, and usefulness of EUS in esophageal varices were discussed in UGI sessions. In the PB part, pancreatic cystic lesions, EUS-guided biliopancreatic drainage, EUS-guided tissue acquisition, and improvement of diagnostic yield in indeterminate biliary lesions by using intraductal ultrasound were discussed. Advanced techniques such as contrast-enhanced EUS, EUS elastography and forward-viewing echoendoscopy were also discussed. In this paper, I focused mainly on topics of UGI and briefly mentioned about advanced EUS techniques since more EUS related papers by other invited speakers were presented afterwards.
Endosonography; Early gastrointestinal cancer; Subepithelial lesion; Technique
Introduction of endoscopic ultrasound (EUS) to medical practice has brought a huge change in diagnostic algorithm of many gastrointestinal diseases. Addition of EUS-guided fine needle aspiration (FNA) upgraded diagnostic power of EUS. In this focused review series, value of EUS-FNA in the diagnosis of various diseases and tips for getting the best results with EUS-FNA are described by four invited authors including myself. First, Dr. Jeong Seop Moon discussed about EUS-FNA in submucosal lesion. He also touched on basic techniques and needles of EUS-FNA in his article. Next, I focused on additional value of EUS-FNA in the staging of hollow viscus cancer to optimize the treatment strategy. World's well-known endosonographer, Dr. Robert H. Hawes kindly presented his profound thoughts on EUS-FNA in pancreatic cystic lesions. Dr. Jayapal Ramesh and Dr. Shyam Varadarajulu shared their valuable tips for getting the best results when using EUS-FNA. Nobody doubts now EUS-FNA is an indispensable procedure in gastrointestinal endoscopy. Therefore, this focused review series will provide the readers with the concentrated knowledge of "What should we know about EUS-FNA."
Endosonography; Fine-needle biopsy; Aspiration; Technique
Accurate cancer staging is essential in patients with hollow viscus malignancy to decide therapeutic modalities. Endoscopic ultrasound (EUS) is considered as the best modality for local staging of hollow viscus cancer. EUS-guided fine needle aspiration (FNA) is a minimally invasive and effective sampling method. EUS-FNA should be applied when positive diagnosis of malignancy can possibly change the choice of therapeutic options. EUS in conjunction with EUS-FNA can optimize stage-directed therapy which is helpful in selecting minimally invasive treatment option including endoscopic treatment and avoiding unnecessary surgery in advanced cases.
Endosonography; Fine needle biopsy; Staging; Neoplasms
Gossypiboma refers to a mass resulting from a retained gauze pad accidentally left within the body after surgery. Although the clinical features are diverse, it is often found incidentally as a mass having an internal cystic change and adhesion to adjacent organs. Abdominal computed tomography (CT) is helpful, yet the initial diagnosis can be misleading in cases with atypical findings. We report a case of gossypiboma in a 78-year-old woman that we suspected was a gastrointestinal stromal tumor according to abdominal CT and endoscopic ultrasound, yet was diagnosed as a gossypiboma postoperatively.
Gossypiboma; Endoscopic ultrasonography; Gastrointestinal stromal tumor
Endoscopic submucosal dissection (ESD) is becoming a popular procedure for the diagnosis and treatment of superficial mucosal lesions, and has the advantage of en bloc resection which yields a higher complete resection and remission rate compared to endoscopic mucosal resection (EMR). However, the learning process of this advanced endoscopic procedure requires a lengthy training period and considerable experience to be proficient. A well framed training protocol which is safe, effective, easily reproducible and cost-effective is desirable to teach ESD. In addition, the training course may need to be tailored around settings such as ethnicity, culture, workload, and disease incidence. In Asian countries with a large volume of early gastric lesions which need endoscopic treatment, endoscopists would be able to learn ESD expanding their skills from EMR to ESD under the supervision of experts. Whereas, in Western countries due to the low incidence of superficial gastric tumors, trials have utilized simulator models to improve learning. In Korea, the Korean Society of Gastrointestinal Endoscopy (KSGE) is playing an important role in training many gastroenterologists who have shown an interest in performing ESD by providing an annual live demonstration and a nationwide tutoring program. The purpose of this article is to introduce our ESD tutoring experience, review the published papers related to this topic, and propose several suggestions for future directions in teaching and learning ESD.
Endoscopic submucosal dissection; Learning; Teaching
In South Korea, health check-ups are readily accessible to the public. We aimed to compare the prevalence of upper gastrointestinal (GI) and lower GI diseases in Korean Americans and native Koreans to determine differences and risk factors.
In total, 1,942 subjects who visited Gangnam Severance Hospital from July 2008 to November 2010 for a health check-up were enrolled. Basic characteristics and laboratory data for the subjects were collected. Esophagogastroduodenoscopy and colonoscopy were performed. In total, 940 Korean Americans (group 1) and 1,002 native Koreans (group 2) were enrolled.
The overall prevalence of GI diseases for each group (group 1 vs group 2) were as follows: reflux esophagitis (RE) (9.65% vs 7.9%), gastric ulcer (2.8% vs 3.4%), duodenal ulcer (2.3% vs 3.6%), gastric cancer (0.4% vs 0.3%), colorectal polyp (35.9% vs 35.6%), colorectal cancer (0.5% vs 0.5%), and hemorrhoids (29.4% vs 21.3%). The prevalence of hemorrhoids was significantly higher in group 1 than in group 2 (p=0.001). In the multivariable analysis of group 1, male sex, age over 50 years, hypercholesterolemia and hypertriglyceridemia predicted colorectal polyps. Male sex and high fasting glucose levels were associated with RE.
Our study showed that the prevalence of GI diseases (except hemorrhoids) in Korean Americans was similar to that observed in native Koreans. Therefore, the Korean guidelines for upper and lower screening endoscopy may be applicable to Korean Americans.
Korean Americans; Screening endoscopy
Rapid advances in the technology of gastrointestinal endoscopy as well as the evolution of science have made it necessary for us to continue update in either various endoscopic techniques or state of art lectures relevant to endoscopy. International Digestive Endoscopy Network (IDEN) 2013 was held in conjunction with Korea-Japan Joint Symposium on Gastrointestinal Endoscopy (KJSGE) during June 8 to 9, 2013 at Seoul, Korea. Two days of impressive scientific program dealt with a wide variety of basic concerns from upper gastrointestine (GI), lower GI, pancreaticobiliary endoscopy to advanced knowledge including endoscopic submucosal dissection forum. IDEN seems to be an excellent opportunity to exchange advanced information of the latest issues on endoscopy with experts from around the world. In this special issue of Clinical Endoscopy, we prepared state of art review articles from contributing authors and the current highlights will skillfully deal with very hot spots of each KJSGE, upper GI, lower GI, and pancreaticobiliary sessions by associated editors of Clinical Endoscopy.
International Digestive Endoscopy Network; Korean Society of Gastrointestinal Endoscopy; Japan Gastrointestinal Endoscopy Society; Highlight; Clinical Endoscopy
Brown adipocytes play an important role in regulating the balance of energy, and as such, there is a strong correlation between obesity and the amount of brown adipose tissue. Although the molecular mechanism underlying white adipocyte differentiation has been well characterized, brown adipocyte differentiation has not been studied extensively. Here, we investigate the potential role of dual-specificity phosphatase 10 (DUSP10) in brown adipocyte differentiation using primary brown preadipocytes.
Methods and Results
The expression of DUSP10 increased continuously after the brown adipocyte differentiation of mouse primary brown preadipocytes, whereas the phosphorylation of p38 was significantly upregulated at an early stage of differentiation followed by steep downregulation. The overexpression of DUSP10 induced a decrease in the level of p38 phosphorylation, resulting in lower lipid accumulation than that in cells overexpressing the inactive mutant DUSP10. The expression levels of several brown adipocyte markers such as PGC-1α, UCP1, and PRDM16 were also significantly reduced upon the ectopic expression of DUSP10. Furthermore, decreased mitochondrial DNA content was detected in cells expressing DUSP10. The results obtained upon treatment with the p38 inhibitor, SB203580, clearly indicated that the phosphorylation of p38 at an early stage is important in brown adipocyte differentiation. The effect of the p38 inhibitor was partially recovered by DUSP10 knockdown using RNAi.
These results suggest that p38 phosphorylation is controlled by DUSP10 expression. Furthermore, p38 phosphorylation at an early stage is critical in brown adipocyte differentiation. Thus, the regulation of DUSP10 activity affects the efficiency of brown adipogenesis. Consequently, DUSP10 can be used as a novel target protein for the regulation of obesity.
Thioredoxin-interacting protein (Txnip) regulates intracellular redox state and prompts oxidative stress by binding to and inhibiting Thioredoxin (Trx). In addition, via a Trx-independent mechanism, Txnip regulates glucose metabolism and thus maintains intracellular glucose levels. Previously, we found Txnip mRNA highly expressed in immature germinal vesicle (GV) oocytes, but currently there is no report describing the role of Txnip in oocytes. Therefore, we conducted the present study to determine the function of Txnip in mouse oocytes' maturation and meiosis by using RNA interference (RNAi) method. Upon specific depletion of Txnip, 79.5% of oocytes were arrested at metaphase I (MI) stage. Time-lapse video microscopy analysis revealed that the formation of granules in the oocyte cytoplasm increased concurrent with retarded cytoplasmic streaming after Txnip RNAi treatment. Txnip RNAi-treated oocytes had upregulated glucose uptake and lactate production. To confirm the supposition that mechanism responsible for these observed phenomena involves increased lactate in oocytes, we cultured oocytes in high lactate medium and observed the same increased granule formation and retarded cytoplasmic streaming as found by Txnip RNAi. The MI-arrested oocytes exhibited scattered microtubules and aggregated chromosomes indicating that actin networking was disturbed by Txnip RNAi. Therefore, we conclude that Txnip is a critical regulator of glucose metabolism in oocytes and is involved in maintaining cytoplasmic streaming in mouse oocytes.
Methicillin-resistant Staphylococcus aureus (MRSA) is recognized as an important cause of not only hospital acquired pneumonia, but also non-nosocomial pneumonia. However, the risk factors for non-nosocomial MRSA pneumonia are not clearly defined. Our objective was to identify risk factors at admission that were associated with non-nosocomial MRSA pneumonia.
We evaluated 943 patients admitted to a university-affiliated hospital with culture-positive bacterial pneumonia developed outside the hospital from January 2008 to December 2011. We compared the clinical characteristics between MRSA and non-MRSA pneumonia, and identified risk factors associated with MRSA pneumonia.
Of 943 patients, MRSA was identified in 78 (8.2%). Higher mortality was observed in MRSA than in non-MRSA patients (33.3% vs. 21.5%; P = 0.017). In a logistic regression analysis, MRSA pneumonia was observed more frequently in patients with a previous history of MRSA infection (OR = 6.05; P < 0.001), a PSI score ≥120 (OR = 2.40; P = 0.015), intravenous antibiotic treatment within 30 days of pneumonia (OR = 2.23; P = 0.018). By contrast, non-MRSA pneumonia was observed more often in patients with a single infiltrate on chest radiography (OR = 0.55; P = 0.029).
Anti-MRSA antibiotics could be considered in hospitalized non-nosocomial patients with several risk factors identified herein. The presence or absence of these factors would provide useful guidance in selecting initial empirical antibiotics.
Pneumonia; Methicillin-resistant Staphylococcus aureus; Non-nosocomial; Risk factors; Community-acquired pneumonia; Healthcare-associated pneumonia
In somatic cell nuclear transfer (SCNT) procedures, exquisite enucleation of the recipient oocyte is critical to cloning efficiency. The purpose of this study was to compare the effects of two enucleation systems, Hoechst staining and UV irradiation (hereafter, irradiation group) and Oosight imaging (hereafter, Oosight group), on the in vitro production of bovine SCNT embryos. In the Oosight group, the apoptotic index (2.8±0.5 vs. 7.3±1.2) was lower, and the fusion rate (75.6% vs. 62.9%), cleavage rate (78.0% vs. 63.7%), blastocyst rate (40.2% vs. 29.2%), and total cell number (128.3±4.8 vs. 112.2±7.6) were higher than those in the irradiation group (all p<0.05). The overall efficiency after SCNT was twice as high in the Oosight group as that in the irradiation group (p<0.05). The relative mRNA expression levels of Oct4, Nanog, Interferon-tau, and Dnmt3A were higher and those of Caspase-3 and Hsp70 were lower in the Oosight group compared with the irradiation group (p<0.05). This is the first report to show the positive effect of the Oosight imaging system on molecular gene expression in the SCNT embryo. The Oosight imaging system may become the preferred choice for enucleation because it is less detrimental to the developmental potential of bovine SCNT embryos.
The Vif protein of human immunodeficiency virus type 1 (HIV-1) promotes viral replication by downregulation of the cell-encoded, antiviral APOBEC3 proteins. These proteins exert their suppressive effects through the inhibition of viral reverse transcription as well as the induction of cytidine deamination within nascent viral cDNA. Importantly, these two effects have not been characterized in detail in human CD4+ T cells, leading to controversies over their possible contributions to viral inhibition in the natural cell targets of HIV-1 replication. Here we use wild-type and Vif-deficient viruses derived from the CD4+ T cells of multiple donors to examine the consequences of APOBEC3 protein function at natural levels of expression. We demonstrate that APOBEC3 proteins impart a profound deficiency to reverse transcription from the initial stages of cDNA synthesis, as well as excessive cytidine deamination (hypermutation) of the DNAs that are synthesized. Experiments using viruses from transfected cells and a novel method for mapping the 3′ termini of cDNAs indicate that the inhibition of reverse transcription is not limited to a few specific sites, arguing that APOBEC3 proteins impede enzymatic processivity. Detailed analyses of mutation spectra in viral cDNA strongly imply that one particular APOBEC3 protein, APOBEC3G, provides the bulk of the antiviral phenotype in CD4+ T cells, with the effects of APOBEC3F and APOBEC3D being less significant. Taken together, we conclude that the dual mechanisms of action of APOBEC3 proteins combine to deliver more effective restriction of HIV-1 than either function would by itself.
Occurrence of dynamic left ventricular outflow tract (LVOT) obstruction is not infrequent in critically ill patients, and it is associated with potential danger. Here, we report a case of transient heart failure with hemodynamic deterioration paradoxically induced by extreme dehydration. This article describes clinical features of the patient and echocardiographic findings of dynamic LVOT obstruction and significant mitral regurgitation caused by systolic anterior motion of the mitral valve in a volume-depleted heart.
Dynamic obstruction; mitral regurgitation; shock; dehydration; echocardiography
Little information is available on the use of chest computed tomography (CT) to predict breast tumor size in breast cancer, despite the fact that chest CT examinations are being increasingly used. The purpose of this study was to evaluate the value of chest CT for predicting breast tumor size using pathology measurements as reference standards.
Tumor sizes (defined as greatest diameter) were retrospectively measured on the preoperative chest CT images of 285 patients with surgically proven unifocal, invasive breast carcinoma. Greatest tumor diameters as determined by chest CT and pathologic examinations were compared by linear regression and Spearman’s rho correlation analysis. Concordance between CT and pathology results was defined as a diameter difference of <5 mm. Subgroup analyses were also performed with respect to tumor size (<20 mm or ≥20 mm) and histological subtype (invasive ductal carcinoma(IDC) or non-IDC).
CT and pathology measured diameters were found to be linearly related (size at pathology = 1.086 × CT determined tumor size - 1.141; Spearman’s rho correlation coefficient = 0.84, P<0.001). Most tumors (n = 228, 80.0%) were concordant by chest CT and pathology, but 36 tumors (12.7%) were underestimated by CT (average underestimation, 11 mm; range, 6–36 mm) and 21 tumors (7.4%) were overestimated (average overestimation by CT, 10 mm; range, 6–19 mm). The concordance rate between the two sets of measurements was greater for tumor of <20 mm and for IDC (P<0.001 and P = 0.011, respectively).
Tumor size by chest CT is well correlated with pathology determined tumor size in breast cancer patients, and the diameters of the majority of tumors by chest CT and pathology differed by <5 mm. In addition, the concordance rate was higher for breast tumors of <20 mm and for tumors of the IDC histologic subtype.
Breast cancer; Chest CT; Tumor size; Pathology
We investigated gender differences in event-related potential (ERP) responses to subliminally presented threat-related stimuli.
Twenty-four participants were presented with threat-related and neutral pictures for a very brief period of time (17 ms). To explore gender differences in ERP responses to subliminally presented stimuli, we examined six ERP components [P1, N170, N250, P300, Early Posterior Negativity (EPN) and Late Positive Potential (LPP)].
The result revealed that only female participants showed significant increases in the N170 and the EPN in response to subliminally presented threat-related stimuli compared to neutral stimuli.
Our results suggest that female participants exhibit greater cortical processing of subliminally presented threat-related stimuli than male participants.
Threat-related stimuli; Gender; Subliminal stimuli; N170; EPN
We attempted to identify the presence of a so called 'March effect (or phenomenon)' (which had long been known as a 'July effect' in western countries), a transient increase in adverse outcomes during an unskilled period for new interns and residents in a teaching hospital, among a cohort of patients with spontaneous subarachnoid hemorrhage (sSAH).
A total of 455 consecutive patients with sSAH from our department database from 2008 to 2010 were enrolled retrospectively and the admission month, patient demographics and clinical characteristics, treatment modalities and discharge outcomes were analyzed. Multivariate regression analysis was used to determine whether unfavorable discharge and in-hospital mortality showed a significant increase during the unskilled months for new interns and residents (from March to May) in a pattern suggestive of a "March effect".
Among 455 patients with sSAH, 113 patients were treated during the unskilled period (from March to May) and the remaining 342 patients were treated during the skilled period (from June until February of the next year). No statistically significant difference in demographics and clinical characteristics was observed between patients treated during these periods. In addition, the mortality and unfavorable discharge rates of the un-skilled period were 16.8% and 29.7% and those of the skilled period were 15.5% and 27.2%, respectively. However, no statistically significant difference was observed between them.
Findings of our study suggest that there was no 'March effect' on the mortality rate and unfavorable discharge rate among patients with sSAH in our hospital during the study period.
Spontaneous subarachnoid hemorrhage; March effect; Mortality rate; July effect; Teaching hospital
Colorectal polyps of mesenchymal origin are a rare group of colorectal disorders. A "mucosal Schwann-cell hamartoma," which is one type of polypoid lesion that originates from the mesenchyme, is a newly-proposed disease entity to be distinguished from the neurofibromas found in type-1 neurofibromatosis. This lesion is composed of pure Schwann-cell proliferation in the lamina propria and shows diffuse immunoreactivity for the S-100 protein. We report a case of a polypoid lesion of the colon with the features of this recently-proposed disease entity.
Schwann cells; Hamartoma; Neurofibroma; Neuroma; Colon polyps
We investigated the incidence and clinical characteristics of renal cell carcinoma (RCC) in the native kidney of renal transplant recipients.
Between 1991 and 2010, 1,425 patients underwent kidney transplantation at our institution. We retrospectively evaluated the clinical features and outcomes in renal transplant patients with RCC in the native kidney after renal transplantation.
The patients included three males and two females with a mean age of 63 years (range, 52 to 74). The incidence of RCC was 0.35%. The median interval between renal transplantation and RCC occurrence was 16.2 years (range, 9 to 20). All of our patients with RCC had developed renal cysts either before (n = 3) or after (n = 2) renal transplantation. The mean duration of dialysis was 12 months (range, 2 to 39). Of the five patients, four underwent dialysis treatment for less than 8 months. All the RCCs were low grade at the time of diagnosis. Four patients underwent radical nephrectomy, and one patient refused the operation. The four patients who underwent radical nephrectomy showed no evidence of local recurrence or distant metastasis during the median follow-up of 2.9 years. However, the patient who did not undergo surgery developed spinal metastasis from the RCC 6 years later.
This study suggests that the follow-up period is an important factor for the development of RCC in renal transplant recipients, and more vigorous screening with a longer follow-up period is required in renal transplant recipients.
Kidney transplantation; Nephrectomy; Carcinoma, renal cell
Fluoroquinolones are an important class of antibiotics that are widely used in adult patients because of their broad spectrum of activity, good tissue penetration, and oral bioavailability. However, fluoroquinolone use in children is limited because juvenile animals developed arthropathy in previous experiments on fluoroquinolone use. Indications for fluoroquinolone use in patients younger than 18 years, as stated by the U.S. Food and Drug Administration, include treatment of complicated urinary tract infections and postexposure treatment for inhalation anthrax. In Korea, the systemic use of fluoroquinolones has not been approved in children younger than 18 years. Although concerns remain regarding the adverse musculoskeletal effects of fluoroquinolones in children, their use in the pediatric population has increased in many circumstances. While pediatricians should be aware of the indications and adverse effects of fluoroquinolones, recent studies have shown that the risk for musculoskeletal complications in children did not significantly increase following fluoroquinolone treatment. In addition, fluoroquinolones may be particularly helpful in treating multidrug-resistant infections that have not responded to standard antibiotic therapy in immunocompromised patients. In the present article, we provide an updated review on the safety and current recommendations for using fluoroquinolones in children.
Fluoroquinolones; Adverse effects; Joint diseases; Child
This special May issue of Clinical Endoscopy discusses the tutorial contents dealing with either the diagnostic or therapeutic gastrointestinal (GI) endoscopy that contain very fundamental and essential points in this filed. The seminar of Korean Society of Gastrointestinal Endoscopy (KSGE) had positioned as one of prime educational seminars covering the very beginner to advanced experts of GI endoscopy. Besides of four rooms allocated for each lecture, two additional rooms were open for either live demonstration or hands-on course, covering totally 20 sessions including one special lecture. Among these prestigious lectures, 12 lectures were selected for the current review articles in this special issue of Clinical Endoscopy journal. Basic course for beginner to advanced tips to expert were all covered in this seminar. This introductory review prepared by four associated editors of Clinical Endoscopy contained core contents divided into four sessions-upper gut, lower gut, pancreaticobiliary, and specialized topic session part-to enhance understandings not covered by enlisted review articles in this issue.
Clinical endoscopy; Seminar; Hands-on course; Highlight
Neuronal activity is critical for the formation and modification of neural circuits during brain development. In hippocampal CA1 pyramidal dendrites, A-type voltage-gated K+ currents, formed primarily by Kv4.2 subunits, control excitability. Here we used Kv4.2 knock-out (Kv4.2-KO) mice along with acute in-vivo expression of Kv4.2 or its dominant negative pore mutant to examine the role of Kv4.2 in the development of CA1 synapses. We found that Kv4.2 expression induces synaptic maturation in juvenile WT mice and rescues developmentally delayed synapses in adult Kv4.2-KO mice. In addition, we show that NMDAR subunit composition can be reverted back to the juvenile form in WT adult synapses by functionally down-regulating Kv4.2 levels. These results suggest that Kv4.2 regulation of excitability determines synaptic maturation state, which can be bidirectionally adjusted into adulthood.
NMDA receptors; AMPA receptors; Kv4.2; voltage-gated potassium channel; synaptic development; hippocampus