CORE B - This program project will investigate the effects of thoracic level spinal cord transection on lower urinary tract dysfunction using various animal models based on C57BL/10 mice (Projects 1, 2 and 3) and Sprague Dawley rats (Project 4). These models include spinal cord transected, pudendal nerve cut and ureter diverted adult mice or rats, neonatal rats and matched controls. The different projects will also use models and controls where the bladder, dorsal root ganglia or striated external urethral sphincter is injected with pseudorabies virus (PRV) linked with the genetically encoded Ca2+-indicator, GCaMP4, or GFP or RFP fluorescent indicators. PRV only transfects nerves and, depending upon the viral strain, is transported by the afferent or efferent nerves to dorsal root ganglia or spinal motoneurons in only a retrograde direction, or both retrograde and anteriograde directions. Within the spinal cord, PRV crosses synapses and is transported transneuronally in a retrograde manner to interneurons located at upstream sites on reflex pathways Animal Core B will secure and maintain the animals for the different projects. Animal orders, surgeries, postoperative care and record keeping will be carried out by the fulltime Assistant Core Director. The optimal animal numbers for each set of experiments have been determined and will continue to be adjusted with the assistance of the program's experienced statistician and his assistant. Thus, the animal core will offer the advantages of reproducibility, ease of data comparison across projects and time- and cost-effectiveness. These advantages will be further enhanced by the different projects using multiple tissues from the same animals. Animal Core B will closely interact with Imaging Core A and the project directors to effectively schedule animal preparation and usage.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Program Projects (P01)
Project #
1P01DK093424-01A1
Application #
8463701
Study Section
Special Emphasis Panel (ZDK1-GRB-6 (O1))
Project Start
Project End
Budget Start
2013-08-20
Budget End
2014-07-31
Support Year
1
Fiscal Year
2013
Total Cost
$247,279
Indirect Cost
$85,129
Name
University of Pittsburgh
Department
Type
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Kullmann, F Aura; Beckel, Jonathan M; McDonnell, Bronagh et al. (2018) Involvement of TRPM4 in detrusor overactivity following spinal cord transection in mice. Naunyn Schmiedebergs Arch Pharmacol 391:1191-1202
Zabbarova, Irina V; Ikeda, Youko; Carder, Evan J et al. (2018) Targeting p75 neurotrophin receptors ameliorates spinal cord injury-induced detrusor sphincter dyssynergia in mice. Neurourol Urodyn 37:2452-2461
Shimizu, Nobutaka; Wada, Naoki; Shimizu, Takahiro et al. (2018) Effects of nerve growth factor neutralization on TRP channel expression in laser-captured bladder afferent neurons in mice with spinal cord injury. Neurosci Lett 683:100-103
Ryu, Jae Cheon; Tooke, Katharine; Malley, Susan E et al. (2018) Role of proNGF/p75 signaling in bladder dysfunction after spinal cord injury. J Clin Invest 128:1772-1786
Wada, Naoki; Shimizu, Takahiro; Shimizu, Nobutaka et al. (2018) The effect of neutralization of nerve growth factor (NGF) on bladder and urethral dysfunction in mice with spinal cord injury. Neurourol Urodyn :
Shimizu, Nobutaka; Doyal, Mark F; Goins, William F et al. (2018) Corrigendum to 'Morphological Changes in Different Populations of Bladder Afferent Neurons Detected by Herpes Simplex Virus (HSV) Vectors with Cell-type-specific Promoters in Mice with Spinal Cord Injury' [Neuroscience 364 (2017) 190-201]. Neuroscience 381:161
Beckel, Jonathan M; de Groat, William C (2018) The effect of the electrophilic fatty acid nitro-oleic acid on TRP channel function in sensory neurons. Nitric Oxide :
Ikeda, Youko; Zabbarova, Irina V; Birder, Lori A et al. (2018) Relaxin-2 therapy reverses radiation-induced fibrosis and restores bladder function in mice. Neurourol Urodyn 37:2441-2451
Shimizu, Takahiro; Majima, Tsuyoshi; Suzuki, Takahisa et al. (2018) Nerve growth factor-dependent hyperexcitability of capsaicin-sensitive bladder afferent neurones in mice with spinal cord injury. Exp Physiol 103:896-904
Kullmann, F A; Chang, H H; Gauthier, C et al. (2018) Serotonergic paraneurones in the female mouse urethral epithelium and their potential role in peripheral sensory information processing. Acta Physiol (Oxf) 222:

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