International Neurourology Journal最新文献

{"title":"Human Endogenous Retroviruses: Friends and Foes in Urology Clinics.","authors":"Sun-Kyung Lee,&nbsp;Seung Hyun Kim,&nbsp;Joohong Ahnn","doi":"10.5213/inj.2244284.142","DOIUrl":"https://doi.org/10.5213/inj.2244284.142","url":null,"abstract":"<p><p>Human endogenous retroviruses (HERVs) are originated from ancient exogenous retroviruses, which infected human germ line cells millions of years ago. HERVs have generally lost their replication and retrotransposition abilities, but adopted physiological roles in human biology. Though mostly inactive, HERVs can be reactivated by internal and external factors such as inflammations and environmental conditions. Their aberrant expression can participate in various human malignancies with complex etiology. This review describes the features and functions of HERVs in urological subjects, such as urological cancers and human reproduction. It provides the current knowledge of the HERVs and useful insights helping practice in urology clinics.</p>","PeriodicalId":14466,"journal":{"name":"International Neurourology Journal","volume":"26 4","pages":"275-287"},"PeriodicalIF":2.3,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/b0/8b/inj-2244284-142.PMC9816444.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10520020","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stress-Induced Changes in Trophic Factor Expression in the Rodent Urinary Bladder: Possible Links With Angiogenesis.","authors":"Mathijs M de Rijk,&nbsp;Amanda Wolf-Johnston,&nbsp;Aura F Kullmann,&nbsp;Katherine Maringer,&nbsp;Sunder Sims-Lucas,&nbsp;Gommert A van Koeveringe,&nbsp;Larissa V Rodríguez,&nbsp;Lori A Birder","doi":"10.5213/inj.2244118.059","DOIUrl":"https://doi.org/10.5213/inj.2244118.059","url":null,"abstract":"<p><strong>Purpose: </strong>Substantive evidence supports a role of chronic stress in the development, maintenance, and even enhancement of functional bladder disorders such as interstitial cystitis/bladder pain syndrome (IC/BPS). Increased urinary frequency and bladder hyperalgesia have been reported in rodents exposed to a chronic stress paradigm. Here, we utilized a water avoidance stress (WAS) model in rodents to investigate the effect of chronic stress on vascular perfusion and angiogenesis.</p><p><strong>Methods: </strong>Female Wistar-Kyoto rats were exposed to WAS for 10 consecutive days. Bladder neck tissues were analyzed by western immunoblot for vascular endothelial growth factor (VEGF) and nerve growth factor precursor (proNGF). Vascular perfusion was assessed by fluorescent microangiography followed by Hypoxyprobe testing to identify regions of tissue hypoxia.</p><p><strong>Results: </strong>The expression of VEGF and proNGF in the bladder neck mucosa was significantly higher in the WAS rats than in the controls. There was a trend toward increased vascular perfusion, but without a statistically significant difference from the control group. The WAS rats displayed a 1.6-fold increase in perfusion. Additionally, a greater abundance of vessels was observed in the WAS rats, most notably in the microvasculature.</p><p><strong>Conclusion: </strong>These findings show that chronic psychological stress induces factors that can lead to increased microvasculature formation, especially around the bladder neck, the region that contains most nociceptive bladder afferents. These findings may indicate a link between angiogenesis and other inflammatory factors that contribute to structural changes and pain in IC/BPS.</p>","PeriodicalId":14466,"journal":{"name":"International Neurourology Journal","volume":"26 4","pages":"299-307"},"PeriodicalIF":2.3,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/8f/e4/inj-2244118-059.PMC9816446.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10520021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Commentary on \"Risk Factors for Transurethral Coagulation for Hemostasis During Holmium Laser Enucleation of the Prostate\".","authors":"Pankaj N Maheshwari,&nbsp;Aditya Goyal,&nbsp;Pushkar Shrivastava","doi":"10.5213/inj.2244240.120","DOIUrl":"https://doi.org/10.5213/inj.2244240.120","url":null,"abstract":"Copyright © 2022 Korean Continence Society This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Corresponding author: Pankaj N. Maheshwari https://orcid.org/0000-0002-9055-0238 Fortis Hospital Mulund, Mulund West, Mumbai 400080, India Email: dr.maheshwaripn@gmail.com Submitted: October 9, 2022 / Accepted after revision: November 23, 2022 To the editor, We read the manuscript, ‘Risk factors for transurethral coagulation for hemostasis during holmium laser enucleation of the prostate,’ by Yoon et al. [1] with huge interest. We would like to complement the authors for a large experience in holmium laser enucleation of the prostate (HoLEP) and an interesting account of need of electro-cautery during the procedure. The need for electro-cautery coagulation in 22.8% patients is indeed very high. It was used in about 19.1% to make the vision clearer for morcellation but even 3.7% for bleeding that could not be controlled by laser coagulation is high. HoLEP as a part of management protocol has been available for more than 2 decades and apart from the initial learning curve, electro-coagulation is rarely needed. It is very difficult to agree with the conclusion that the risk of electro-coagulation increases in patients with transitional zone volume &gt;35 mL. HoLEP is indicated for large volume adenoma [2] and the proposed odds ratio for need for coagulation of 5.17 in ≥53.5-mL adenoma appears very high. The very fact that most recent guidelines propose HoLEP as a treatment of choice for large prostate volumes and for patients on antiplatelet or anticoagulant medications is a testament for its coagulation capabilities [3]. The authors presumption that the risk of bleeding increases as the prostate volume increases because the larger the prostate, the more blood supply is required, and thus, the blood vessel density increases may not hold true for HoLEP as in contrast to transurethral resection of the prostate where we resect through the adenoma, during HoLEP the procedure is performed at the capsular level hence the blood vessel density in the prostatic tissue will not have an impact. We would like to provide our tips for reducing bleeding and hence need for electro-coagulation. (1) Use the laser at the highest possible frequency. The simultaneous coagulation is better at higher frequency. (2) During the dissection, it is important to remain on the capsule. The bleeding is more if you cut through the tissue. (3) Bleeding increases if there are capsular perforation. Being aware and avoiding them is important. (4) Dissect by nontouch technique by the plasma of the laser and not by direct cutting. (5) If bleeding is still there, a catheter with light traction and irrigation for a few minutes controls most bleedin","PeriodicalId":14466,"journal":{"name":"International Neurourology Journal","volume":"26 4","pages":"353-354"},"PeriodicalIF":2.3,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/d5/39/inj-2244240-120.PMC9816445.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10520023","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oxidative Stress and Its Relation to Lower Urinary Tract Symptoms.","authors":"Karl-Erik Andersson","doi":"10.5213/inj.2244190.095","DOIUrl":"10.5213/inj.2244190.095","url":null,"abstract":"<p><p>The aim of this review is to discuss how to link lower urinary tract symptoms (LUTS) and oxidative stress (OS) and to define relevant targets for therapeutic intervention. Narrative review based on published literature. Many of the multifactorial pathophysiological mechanisms behind LUTS can initiate reactive oxygen species (ROS) generation. Assuming that OS is a consequence rather than a primary cause of LUTS it seems reasonable to identify both the disease mechanism initiating LUTS, and the source of ROS involved. There are many possible sources of ROS overproduction, but the NADPH oxidase (NOX) family of enzymes is the primary source; NOX activation in turn, may result in the activation of secondary ROS sources, i.e., ROS-dependent ROS production. Selective NOX inhibition therefore seems an attractive therapeutic strategy in LUTS treatment. The finding of NOX2 localization to centers in the brain associated with micturition control, opens up for further studies of NOX involvement in the central control of micturition, normally and in disease. Further information on the localization of the different isoforms of NOX in the LUT e.g., the bladder wall and its components and the prostate, is desirable. To optimize treatment, the pathophysiological mechanism initiating LUTS, and the activated isoform of NOX, should be identified. Unfortunately, in most cases of LUTS this is currently not possible. Even if selective NOX inhibitors have entered the clinical trial stage for treatment of disorders other than LUT dysfunction, their efficacy for LUTS treatment has to be demonstrated. If this can be achieved, an attractive approach would be combination of selective NOX inhibition with established drug therapies.</p>","PeriodicalId":14466,"journal":{"name":"International Neurourology Journal","volume":"26 4","pages":"261-267"},"PeriodicalIF":1.8,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/2a/de/inj-2244190-095.PMC9816449.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10510629","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interstitial Cystitis: A Consequence of Weakened Uterosacral Ligaments Failing to Support Visceral Plexuses and Bladder Stretch Receptors, and Therefore Potentially Curable?","authors":"Peter Petros","doi":"10.5213/inj.2142366.183","DOIUrl":"https://doi.org/10.5213/inj.2142366.183","url":null,"abstract":"Copyright © 2022 Korean Continence Society This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Corresponding author: Peter Petros https://orcid.org/0000-0002-9611-3258 University of Western Australia School of Mechanical and Mathematical Engineering, Perth, Australia Email: pp@kvinno.com *Current status: retired pelvic floor surgeon. Submitted: November 29, 2021 / Accepted after revision: June 9, 2022 To the editor, I read the state-of-the-art review of interstitial cystitis/bladder pain syndrome (IC/BPS) by Ueda et al. [1] with great interest. An erudite, scholarly paper, it states there is a crisis as regards IC—namely, there has been no progress for 25 years. The authors concluded [1], “Thus, there can be no bright future for IC/BPS without these 3 steps: (1) understanding the symptoms, (2) detecting abnormal findings in or outside the bladder, and (3) verifying that the abnormality is the cause of the symptoms” [1]. This commentary aims to address their statements, first by introducing an important discovery to International Neurourology Journal readers, Dr. Scheffler’s histologically validated cure of IC/BPS with Hunner ulcer (nonulcerating) [2], and then by discussing its implications relevant to those 3 statements [1]. Scheffler set out to manage a 73-year-old woman with classical posterior fornix syndrome (PFS) symptoms—predictably co-occurring chronic pelvic pain (CPP), urge, abnormal emptying/retention, nocturia, and frequency—caused by laxity of the uterosacral ligaments (USLs) and cured by repair thereof [3], not IC, by repair of cardinal ligaments and USLs, which is the standard cure for PFS [3]. To test whether any relationship exists between PFS and IC [2], we revisited previous data from 46 women with CPP and 171 bladder symptoms, treated for PFS with tissue fixation system (TFS) mini-sling surgery, who fit the International Continence Society (ICS) definition of IC [4]. Their workup [5], included the validated Integral Theory System Questionnaire, preoperative and postoperative urodynamics evaluations, and speculum testing (Fig. 1). The cure rates [5] were 76% for CPP, 74% for urge incontinence, 80% for abnormal emptying/retention, 75% for nocturia 75%, and 50% for frequency. Two women had glomerulations. None had Hunner ulcers. In another study by Wagenlehner et al. [6], among 1,420 women with prolapse and PFS symptoms treated by 2 different posterior sling operations, 599 had CPP, 1,179 had bladder symptoms, and 162 had fecal incontinence. A TFS study by Liedl et al. [7], found that 194 women had CPP, with 881 bladder symptoms that were variously cured. Other data showed small pain/urge symptom deterioration at 5 years [8]. The cure of CPP and bladder symptoms [6-8] was in acco","PeriodicalId":14466,"journal":{"name":"International Neurourology Journal","volume":"26 4","pages":"349-351"},"PeriodicalIF":2.3,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/98/e5/inj-2142366-183.PMC9816441.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10520025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Striatal ZBTB16 Is Associated With Cognitive Deficits in Alzheimer Disease Mice.","authors":"Sangjoon Lee,&nbsp;Tae Kyoo Kim,&nbsp;Ji Eun Choi,&nbsp;Hye-Sun Kim,&nbsp;Heh-In Im","doi":"10.5213/inj.2244254.127","DOIUrl":"https://doi.org/10.5213/inj.2244254.127","url":null,"abstract":"<p><strong>Purpose: </strong>In Alzheimer disease (AD), brain regions such as the cortex and the hippocampus show abundant amyloid load which correlates with cognitive function decline. Prior to the significant development of AD pathophysiology, patients report the manifestation of neuropsychiatric symptoms, indicating a functional interplay between basal ganglia structures and hippocampal regions. Zinc finger and BTB domain-containing protein 16 (ZBTB16) is a transcription factor that controls the expression of downstream genes and the involvement of ZBTB16 in the striatum undergoing pathological aging in AD and the resulting behavioral phenotypes has not yet been explored.</p><p><strong>Methods: </strong>To study molecular alterations in AD pathogenesis, we analyzed the brain from amyloid precursor protein (APP)/ presenilin 1 (PS1) transgenic mice. The molecular changes in the striatal region of the brain were analyzed via the immunoblotting, and the quantitative RNA sequencing. The cognitive impairments of APP/PS1 mice were assessed via 3 behavioral tests: 3-chamber test, Y-maze test, and noble object recognition test. And multielectrode array experiments for the analysis of the neuronal activity of the striatum in APP/PS1 mice was performed.</p><p><strong>Results: </strong>We found that the alteration in ZBTB16 levels that occurred in the early ages of the pathologically aging striatum coalesces with the disruption of transcriptional dysregulation while causing social memory deficits, anxiety-like behavior. The early ZBTB16 knockdown treatment in the striatum of APP/PS1 mice rescued cognition that continued into later age.</p><p><strong>Conclusion: </strong>This study demonstrates that perturbation of transcriptional regulation of ZBTB16 during pathological aging may influence cognitive impairments and reveals a potent approach to targeting the transcriptional regulation of the striatum for the treatment of AD.</p>","PeriodicalId":14466,"journal":{"name":"International Neurourology Journal","volume":"26 Suppl 2","pages":"S106-116"},"PeriodicalIF":2.3,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ba/0a/inj-2244254-127.PMC9767687.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10492761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Changes in the Neuronal Architecture of the Hippocampus in a 6-Hydroxydopamine-Lesioned Rat Model of Parkinson Disease.","authors":"Bohye Kim,&nbsp;Poornima D E Weerasinghe-Mudiyanselage,&nbsp;Mary Jasmin Ang,&nbsp;Jeongmin Lee,&nbsp;Sohi Kang,&nbsp;Jong-Choon Kim,&nbsp;Sung-Ho Kim,&nbsp;Joong-Sun Kim,&nbsp;Chaeyong Jung,&nbsp;Taekyun Shin,&nbsp;Changjong Moon","doi":"10.5213/inj.2244252.126","DOIUrl":"https://doi.org/10.5213/inj.2244252.126","url":null,"abstract":"<p><strong>Purpose: </strong>Parkinson disease (PD) is a progressive neurodegenerative disorder in which dopaminergic (DAergic) systems are destroyed (particularly in the nigrostriatal system), causing both motor and nonmotor symptoms. Hippocampal neuroplasticity is altered in PD animal models, resulting in nonmotor dysfunctions. However, little is known about the precise mechanism underlying the hippocampal dysfunctions in PD.</p><p><strong>Methods: </strong>Striatal 6-hydroxydopamine (6-OHDA) infusions were performed unilaterally in adult Sprague Dawley rats. Both motor and nonmotor symptoms alongside the expression of tyrosine hydroxylase (TH) in the substantia nigra and striatum were confirmed in 6-OHDA-lesioned rats. The neuronal architecture in the hippocampus was analyzed by Golgi staining.</p><p><strong>Results: </strong>During the 7-8 weeks after infusion, the 6-OHDA-lesioned rats exhibited motor and nonmotor dysfunctions (especially anxiety/depression-like behaviors). Rats with unilateral 6-OHDA infusion displayed reduced TH+ immunoreactivity in the ipsilateral nigrostriatal pathway of the brain. Golgi staining revealed that striatal 6-OHDA infusion significantly decreased the dendritic complexity (i.e., number of crossing dendrites, total dendritic length, and branch points) in the ipsilateral hippocampal conus ammonis 1 (CA1) apical/basal and dentate gyrus (DG) subregions. Additionally, the dendritic spine density and morphology were significantly altered in the CA1 apical/basal and DG subregions following striatal 6-OHDA infusion. However, alteration of microglial and astrocytic distributions did not occur in the hippocampus following striatal 6-OHDA infusion.</p><p><strong>Conclusion: </strong>The present study provides anatomical evidence that the structural plasticity in the hippocampus is altered in the late phase following striatal 6-OHDA infusion in rats, possibly as a result of the prolonged suppression of the DAergic system, and independent of neuroinflammation.</p>","PeriodicalId":14466,"journal":{"name":"International Neurourology Journal","volume":"26 Suppl 2","pages":"S94-105"},"PeriodicalIF":2.3,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/0a/01/inj-2244252-126.PMC9767684.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10492757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quantitative Sequencing Analysis of the Striatal Transcriptome in a Mouse Model of Alzheimer Disease.","authors":"Tae Kyoo Kim,&nbsp;Sangjoon Lee,&nbsp;Heh-In Im","doi":"10.5213/inj.2244256.128","DOIUrl":"https://doi.org/10.5213/inj.2244256.128","url":null,"abstract":"<p><strong>Purpose: </strong>The purpose of this study was to analyze the transcriptomic changes in the striatum of amyloid precursor protein/presenilin 1 (APP/PS1) transgenic mice and uncover its association with the methyl-CpG binding protein 2 (MeCP2) mediated-changes in striatal epigenetic signature during Alzheimer disease (AD) pathological progression.</p><p><strong>Methods: </strong>To observe transcriptomic alterations in the striatum before the onset of cognitive impairment in APP/PS1 mice, quantitative 3'mRNA sequencing was performed with RNA extracted from the striatum of 6-month-old and 12-month-old wildtype and APP/PS1 mice. In addition, chromatin immunoprecipitation sequencing was conducted with the DNA from wildtype and APP/PS1 mice of the same age as aforementioned. For transcriptomic analysis, comparison terms were constructed based on aging and transgene expression-normal-aging (12-month-old wildtype/6-month-old wildtype), early-AD (6-month-old APP/PS1/6-month-old wildtype), and late-AD (12-month-old APP/PS1/6-month-old wildtype). To compare the changes in biological pathways and networks, we analyzed gene lists from each comparison term via bioinformatics tools including DAVID (Database for Annotation, Visualization, and Integrated Discovery), STRING (Search Tool for the Retrieval of Interacting Genes/Proteins), and SynGO (Synaptic Gene Ontologies). Furthermore, to assume the effect MeCP2 in AD pathological conditions may have on the transcriptome regulation, analysis of the common genes from Quant-Seq and MeCP2-ChIP-Seq was performed.</p><p><strong>Results: </strong>Enriched pathways including immune system and inflammatory response were confirmed in normal- aging and lateAD, respectively. In particular, enriched pathways of gene expression regulation, transcriptional regulation, and protein catabolic pathways were found to be significantly altered in early-AD. MeCP2-bound genes that were significantly altered in the transcriptome were suggested to be target genes that have a role in the striatum of the early-stage AD model.</p><p><strong>Conclusion: </strong>This study confirmed that the alteration of the striatal transcriptomic profile in APP/PS1 mice was involved with several biological pathways. Additionally, comparative analysis of the transcriptomic changes and the MeCP2 bound regions found that a group of differentially expressed genes may be regulated under the epigenetic control of MeCP2.</p>","PeriodicalId":14466,"journal":{"name":"International Neurourology Journal","volume":"26 Suppl 2","pages":"S117-125"},"PeriodicalIF":2.3,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ce/64/inj-2244256-128.PMC9767686.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10492762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Brain Region-Dependent Alternative Splicing of Alzheimer Disease (AD)-Risk Genes Is Associated With Neuropathological Features in AD.","authors":"Sara Kim,&nbsp;Seonggyun Han,&nbsp;Soo-Ah Cho,&nbsp;Kwangsik Nho,&nbsp;Insong Koh,&nbsp;Younghee Lee","doi":"10.5213/inj.2244258.129","DOIUrl":"https://doi.org/10.5213/inj.2244258.129","url":null,"abstract":"<p><strong>Purpose: </strong>Alzheimer disease (AD) is one of the most complex diseases and is characterized by AD-related neuropathological features, including accumulation of amyloid-β plaques and tau neurofibrillary tangles. Dysregulation of alternative splicing (AS) contributes to these features, and there is heterogeneity in features across brain regions between AD patients, leading to different severity and progression rates; however, brain region-specific AS mechanisms still remain unclear. Therefore, we aimed to systemically investigate AS in multiple brain regions of AD patients and how they affect clinical features.</p><p><strong>Methods: </strong>We analyzed RNA sequencing (RNA-Seq) data obtained from brain regions (frontal and temporal) of AD patients. Reads were mapped to the hg19 reference genome using the STAR aligner, and exon skipping (ES) rates were estimated as percent spliced in (PSI) by rMATs. We focused on AD-risk genes discovered by genome-wide association studies, and accordingly evaluated associations between PSI of skipped exons in AD-risk genes and Braak stage and plaque density mean (PM) for each brain region. We also integrated whole-genome sequencing data of the ascertained samples with RNA-Seq data to identify genetic regulators of feature-associated ES.</p><p><strong>Results: </strong>We identified 26 and 41 ES associated with Braak stage in frontal and temporal regions, respectively, and 10 and 50 ES associated with PM. Among those, 10 were frontal-specific (CLU and NTRK2), 65 temporal-specific (HIF1A and TRPC4AP), and 26 shared ES (APP) that accompanied functional Gene Ontology terms, including axonogenesis in shared-ES genes. We further identified genetic regulators that account for 44 ES (44% of the total). Finally, we present as a case study the systematic regulation of an ES in APP, which is important in AD pathogenesis.</p><p><strong>Conclusion: </strong>This study provides new insights into brain region-dependent AS regulation of the architecture of AD-risk genes that contributes to AD pathologies, ultimately allowing identification of a treatment target and region-specific biomarkers for AD.</p>","PeriodicalId":14466,"journal":{"name":"International Neurourology Journal","volume":"26 Suppl 2","pages":"S126-136"},"PeriodicalIF":2.3,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/db/21/inj-2244258-129.PMC9767683.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10492760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epigenetic Dysfunction of Neurodegenerative Diseases, MeCP2 and More.","authors":"Heh-In Im","doi":"10.5213/inj.2222edi04","DOIUrl":"https://doi.org/10.5213/inj.2222edi04","url":null,"abstract":"Copyright © 2022 Korean Continence Society This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. This quarter’s International Neurourology Journal special issue is “Epigenetic Dysfunction of Neurodegenerative Diseases, MeCP2 and More.” The current issue consists of 3 basic research papers specifically dealing with animal experiments, one on clinical trials, and another utilizing clinical databases. A large part of these papers covers the effects of epigenetic regulation on gene expression and the functional changes of specific brain regions that arise from the pathogenesis of neurodegenerative diseases including Alzheimer disease (AD) and Parkinson disease (PD). In this issue, Lee et al. [1] report that epigenetic changes by MeCP2 may alter ZBTB16 expression in the striatum, and that ZBTB16 function as a transcription factor may influence cognitive decline during AD pathogenesis. Kim et al. [2] performed quantitative sequencing of the early and late-stage AD mouse model striatum and compared the resulting changes in the transcriptome with the dataset from MeCP2 ChIP-Seq. The comparative analysis indicates that certain genes of the transcriptional regulatory pathway could be altered by epigenetic regulators in the course of AD pathogenesis. As a research result highly related to this, Kim et al. [3] shows that neuronal dysfunction in the striatum may lead to structural changes in the hippocampus, suggesting that the functional changes of the striatum in AD and PD are associated with the cognitive decline in neurodegenerative diseases. As an epigenetic mechanism that may affect PD onset, Guhathakurta et al. [4] report the deregulation of the repression mechanism by CpG binding protein TET1 and its downstream effect on SNCA gene expression, implicating SNCA repression as a novel therapeutic strategy for PD. Another posttranscriptional regulation of interest is the alternative splicing of AD-risk genes analyzed by Kim et al. [5]. Here, they identify several novel exon skipping sites according to the frontal and temporal brain regions and proposed them as a treatment target and region-specific biomarker of AD. The epigenetic regulation of gene expression for the maintenance and regulation of brain function is a research field that has recently attracted attention. At the same time, the role of epigenetics in normal aging and neurodegenerative diseases, specifically the functional role of MeCP2 as a brain-enriched epigenetic regulator and the methylation status of the genome have been reported by numerous studies. However, the overarching mechanisms that lead from epigenetic regulation to changes in brain executive function have not yet been fully understood. Thus, in this special issue, we focus on paper","PeriodicalId":14466,"journal":{"name":"International Neurourology Journal","volume":"26 Suppl 2","pages":"S83-84"},"PeriodicalIF":2.3,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/0a/87/inj-2222edi04.PMC9767685.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10492758","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}