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Urothelial neuron

Luke Grundy, Russ Chess-Williams, Stuart M Brierley, Kylie Mills, Kate Hilda Moore, Kylie Mansfield, Roselyn Rose'Meyer, Donna Jayne Sellers, David Grundy
Tachykinins are expressed within bladder innervating sensory afferents and have been shown to generate detrusor contraction and trigger micturition. The release of tachykinins from these sensory afferents may also activate tachykinin receptors on the urothelium, or sensory afferents directly. Here we investigated the direct and indirect influence of tachykinins on mechanosensation by recording sensory signalling from the bladder during distension, urothelial transmitter release ex-vivo, and direct responses to NKA on isolated mouse urothelial cells and bladder-innervating DRG neurons...
June 13, 2018: American Journal of Physiology. Renal Physiology
Steven T Truschel, Dennis R Clayton, Jonathan M Beckel, Jonathan G Yabes, Yi Yao, Amanda Wolf-Johnston, Lori A Birder, Gerard Apodaca
Lysosomal dysfunction is associated with a number of age-related pathologies that affect all organ systems. While much research has focused on neurodegenerative diseases and aging-induced changes in neurons, much less is known about the impact that aging has on lower urinary tract function. Our studies explored age-dependent changes in the content of endo-lysosomal organelles (i.e., multivesicular bodies, lysosomes, and the product of their fusion, endolysosomes) and age-induced effects on lysosomal degradation in the urothelium, the epithelial tissue that lines the inner surface of the bladder, ureters, and renal pelvis...
2018: PloS One
Lori A Birder, F Aura Kullmann
Intense research has focused on the involvement of the nervous system in regard to cellular mechanisms underlying neurogenic inflammation in the pelvic viscera. Evidence supports the neural release of inflammatory factors, trophic factors, and neuropeptides in the initiation of inflammation. However, more recently, non-neuronal cells including epithelia, endothelial, mast cells, and paraneurons are likely important participants in nervous system functions. For example, the urinary bladder urothelial cells are emerging as key elements in the detection and transmission of both physiological and nociceptive stimuli in the lower urinary tract...
May 2018: Seminars in Immunopathology
Luke Grundy, Donna M Daly, Christopher Chapple, David Grundy, Russ Chess-Williams
Both TRPV1 and P2X receptors present on bladder sensory nerve fibres have been implicated in mechanosensation during bladder filling. The aim of this study was to determine possible interactions between these receptors in modulating afferent nerve activity. In wildtype (TRPV1+/+ ) and TRPV1 knockout (TRPV1-/- ) mice, bladder afferent nerve activity, intravesical pressure, and luminal ATP and acetylcholine levels were determined and also intracellular calcium responses of dissociated pelvic DRG neurones and primary mouse urothelial cells (PMUCs)...
January 9, 2018: Scientific Reports
Buffie J Clodfelder-Miller, Hirosato Kanda, Jianguo G Gu, Judy R Creighton, Timothy J Ness, Jennifer J DeBerry
There is mounting evidence underscoring a role for the urothelium in urinary bladder sensation. Previous functional studies have identified bladder primary afferents with mechanosensitive properties suggesting urothelial innervation and/or communication. The current study identifies a group of urothelium-innervating afferent neurons in rat, and characterizes and compares the properties of these and non-urothelial afferent neuron populations. Lumbosacral (LS) primary afferent neurons were retrogradely labeled using intraparenchymal (IPar) microinjection or intravesical (IVes) infusion of tracer into the bladder...
June 15, 2018: Brain Research
Jiaolin Zheng, Dan Yi, Yu Liu, Mingqiu Wang, Yulan Zhu, Huaizhang Shi
Neural stem cells are able to self-renew and generate glial and neuronal lineages. Neural stem cell may serve as therapeutic method for neurological disorders including spinal cord injuries, Parkinson's disease, Huntington's disease and Alzheimer's disease. Long noncoding RNAs (lncRNAs) are longer than 200 nucleotides with limited protein-coding capacity. Recent studies have demonstreated that lncRNAs play an important role in several cellular processes including cell differentiation, cell development, proliferation, apoptosis, invasion and migration...
2017: American Journal of Translational Research
Nicolas Montalbetti, Anna C Rued, Stefanie N Taiclet, Lori A Birder, F Aura Kullmann, Marcelo D Carattino
Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic voiding disorder that presents with pain in the urinary bladder and surrounding pelvic region. A growing body of evidence suggests that an increase in the permeability of the urothelium, the epithelial barrier that lines the interior of the bladder, contributes to the symptoms of IC/BPS. To examine the consequence of increased urothelial permeability on pelvic pain and afferent excitability, we overexpressed in the urothelium claudin 2 (Cldn2), a tight junction (TJ)-associated protein whose message is significantly upregulated in biopsies of IC/BPS patients...
May 2017: ENeuro
J Y Liu, Y B Dai, X Li, K Cao, D Xie, Z T Tong, Z Long, H Xiao, M K Chen, Y L Ye, B Liu, J Tan, J Tang, Z Z Xu, Y Gan, Y H Zhou, F Deng, L Y He
Solute carrier family 12 member 5 (SLC12A5), an integral membrane KCl cotransporter, which maintains chloride homeostasis in neurons, is aberrantly expressed and involved in the tumorigenesis of certain cancers. However, the clinical significance and biological role of SLC12A5 in human bladder urothelial carcinoma (BUC) remains unclear. In this study, the expression of SLC12A5 was examined in clinical specimens of primary BUC and in BUC cell lines using quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR), western blot and immunohistochemistry (IHC)...
March 23, 2017: Cell Death & Disease
Ana Coelho, Tiago Antunes-Lopes, James Gillespie, Francisco Cruz
AIMS: To identify in the human bladder the structures which express the Beta-3 adrenoceptor (β3AR). METHODS: Human bladders from cadaveric organ donors (equally balanced in sex and age) were collected. Bladders were immediately fixed in paraformaldehyde and further processed for cryostat sectioning. Single and double immunohistochemistry was performed using antibodies against β3AR C-terminal, β3AR N-terminal, a pan-neuronal marker (β3-Tubulin) and markers of cholinergic (Vesicular Acetylcholine Transporter), adrenergic (Tyrosine Hidroxylase), and peptidergic (Calcitonin Gene-Related Peptide) nerve fibers...
February 10, 2017: Neurourology and Urodynamics
Hirosato Kanda, Buffie J Clodfelder-Miller, Jianguo G Gu, Timothy J Ness, Jennifer J DeBerry
Pelvic nerve (PN) bladder primary afferent neurons were retrogradely labeled by intraparenchymal (IPar) microinjection of fluorescent tracer or intravesical (IVes) infusion of tracer into the bladder lumen. IPar and IVes techniques labeled two distinct populations of PN bladder neurons differentiated on the basis of dorsal root ganglion (DRG) soma labeling, dye distribution within the bladder, and intrinsic electrophysiological properties. IPar (Fast blue)- and IVes (DiI)-labeled neurons accounted for 91.5% (378...
October 1, 2016: Brain Research
Kendall Morrison, Pia M Challita-Eid, Arthur Raitano, Zili An, Peng Yang, Joseph D Abad, Wendy Liu, Dawn Ratay Lortie, Josh T Snyder, Linnette Capo, Alla Verlinsky, Hector Aviña, Fernando Doñate, Ingrid B J Joseph, Daniel S Pereira, Karen Morrison, David R Stover
SLITRK6 is a member of the SLITRK family of neuronal transmembrane proteins that was discovered as a bladder tumor antigen using suppressive subtractive hybridization. Extensive immunohistochemistry showed SLITRK6 to be expressed in multiple epithelial tumors, including bladder, lung, and breast cancer as well as in glioblastoma. To explore the possibility of using SLITRK6 as a target for an antibody-drug conjugate (ADC), we generated a panel of fully human mAbs specific for SLITRK6. ADCs showed potent in vitro and in vivo cytotoxic activity after conjugation to Monomethyl Auristatin E or Monomethyl Auristatin F...
June 2016: Molecular Cancer Therapeutics
K-X Zhang, Y Matsui, C Lee, O Osamu, L Skinner, J Wang, A So, P S Rennie, W W Jia
Urothelial bladder cancer is the most common malignancy of the urinary tract. Although most cases are initially diagnosed as non-muscle-invasive, more than 80% of patients will develop recurrent or metastatic tumors. No effective therapy exists currently for late-stage metastatic tumors. By intravesical application, local administration of oncolytic Herpes Simplex virus (oHSV-1) can provide a promising new therapy for this disease. However, its inherent neurotoxicity has been a perceived limitation for such application...
2016: Gene Therapy
Anthony Kanai, Christopher Fry, Youko Ikeda, Florenta Aura Kullmann, Brian Parsons, Lori Birder
AIMS: To present a synopsis of the presentations and discussions from Think Tank I, "Implications for afferent-urothelial bidirectional communication" of the 2014 International Consultation on Incontinence-Research Society (ICI-RS) meeting in Bristol, UK. METHODS: The participants presented what is new, currently understood or still unknown on afferent-urothelial signaling mechanisms. New avenues of research and experimental methodologies that are or could be employed were presented and discussed...
February 2016: Neurourology and Urodynamics
Toby C Chai, Andrea Russo, Shan Yu, Ming Lu
The bladder mucosa is comprised of the multilayered urothelium, lamina propria (LP), microvasculature, and smooth muscle fibers (muscularis mucosae). The muscularis mucosae is not always present in the mucosa, and its presence is related to the thickness of the LP. Since there are no mucus secreting cells, "mucosa" is an imprecise term. Nerve fibers are present in the LP of the mucosa. Efferent nerves mediate mucosal contractions which can be elicited by electrical field stimulation (EFS) and various agonists...
October 2016: Autonomic Neuroscience: Basic & Clinical
Isabel Silva, Fátima Ferreirinha, Maria Teresa Magalhães-Cardoso, Miguel Silva-Ramos, Paulo Correia-de-Sá
PURPOSE: Deregulation of purinergic bladder signaling may contribute to persistent detrusor overactivity in patients with bladder outlet obstruction. Activation of uridine diphosphate sensitive P2Y6 receptors increases voiding frequency in rats indirectly by releasing adenosine triphosphate from the urothelium. To our knowledge this mechanism has never been tested in the human bladder. MATERIALS AND METHODS: We examined the role of the uridine diphosphate sensitive P2Y6 receptor on tetrodotoxin insensitive nonneuronal adenosine triphosphate and [(3)H]acetylcholine release from the human urothelium with the lamina propria of control organ donors and patients with benign prostatic hyperplasia...
October 2015: Journal of Urology
K-E Andersson
It is well established that in most species, exocytotic vesicular release of ATP from parasympathetic neurons contributes to contraction of the bladder. However, ATP is released not only from parasympathetic nerves, but also from the urothelium. During bladder filling, the urothelium is stretched and ATP is released from the umbrella cells thereby activating mechanotransduction pathways. ATP release can also be induced by various mediators present in the urine and and/or released from nerves or other components of the lamina propria...
September 2015: Autonomic Neuroscience: Basic & Clinical
Maria-Giuliana Vannucchi, Chiara Traini, Daniele Guasti, Giulio Del Popolo, Maria-Simonetta Faussone-Pellegrini
Urinary bladder voiding is a complex mechanism depending upon interplay among detrusor, urothelium, sensory and motor neurons and connective tissue cells. The identity of some of the latter cells is still controversial. We presently attempted to clarify their phenotype(s) in the human urinary bladder by transmission electron microscopy (TEM) and immunohistochemistry. At this latter aim, we used CD34, PDGFRα, αSMA, c-Kit and calreticulin antibodies. Both, TEM and immunohistochemistry, showed cells that, sharing several telocyte (TC) characteristics, we identified as TC; these cells, however, differed from each other in some ultrastructural features and immunolabelling according to their location...
October 2014: Journal of Cellular and Molecular Medicine
Naoki Yoshimura, Tomohiko Oguchi, Hitoshi Yokoyama, Yasuhito Funahashi, Satoru Yoshikawa, Yoshio Sugino, Naoki Kawamorita, Mahendra P Kashyap, Michael B Chancellor, Pradeep Tyagi, Teruyuki Ogawa
Bladder pain syndrome/interstitial cystitis is a disease with lower urinary tract symptoms, such as bladder pain and urinary frequency, which results in seriously impaired quality of life of patients. The extreme pain and urinary frequency are often difficult to treat. Although the etiology of bladder pain syndrome/interstitial cystitis is still not known, there is increasing evidence showing that afferent hyperexcitability as a result of neurogenic bladder inflammation and urothelial dysfunction is important to the pathophysiological basis of symptom development...
April 2014: International Journal of Urology: Official Journal of the Japanese Urological Association
Warren G Hill
Urine differs greatly in ion and solute composition from plasma and contains harmful and noxious substances that must be stored for hours and then eliminated when it is socially convenient to do so. The urinary tract that handles this output is composed of a series of pressurizable muscular compartments separated by sphincteric structures. With neural input, these structures coordinate the delivery, collection, and, ultimately, expulsion of urine. Despite large osmotic and chemical gradients in this waste fluid, the bladder maintains a highly impermeable surface in the face of a physically demanding biomechanical environment, which mandates recurring cycles of surface area expansion and increased wall tension during filling, followed by rapid wall compression during voiding...
March 6, 2015: Clinical Journal of the American Society of Nephrology: CJASN
Eric J Gonzalez, Lauren Arms, Margaret A Vizzard
Bladder pain syndrome (BPS)/interstitial cystitis (IC) is a chronic pain syndrome characterized by pain, pressure, or discomfort perceived to be bladder related and with at least one urinary symptom. It was recently concluded that 3.3-7.9 million women (>18 years old) in the United States exhibit BPS/IC symptoms. The impact of BPS/IC on quality of life is enormous and the economic burden is significant. Although the etiology and pathogenesis of BPS/IC are unknown, numerous theories including infection, inflammation, autoimmune disorder, toxic urinary agents, urothelial dysfunction, and neurogenic causes have been proposed...
2014: BioMed Research International
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