Molecular Characterization of Non-Neurogenic and Neurogenic Lower Urinary Tract Dysfunction (LUTD) in SCI-Induced and Partial Bladder Outlet Obstruction Mouse Models
We examined bladder function following spinal cord injury (SCI) by repeated urodynamic investigation (UDI), including external urethral sphincter (EUS) electromyography (EMG) in awake restrained mice and correlated micturition parameters to gene expression and morphological changes in the bladder. A...
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MDPI AG
2023-01-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/3/2451 |
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| author | Michelle von Siebenthal Akshay Akshay Mustafa Besic Marc P. Schneider Ali Hashemi Gheinani Fiona C. Burkhard Katia Monastyrskaya |
| author_facet | Michelle von Siebenthal Akshay Akshay Mustafa Besic Marc P. Schneider Ali Hashemi Gheinani Fiona C. Burkhard Katia Monastyrskaya |
| author_sort | Michelle von Siebenthal |
| collection | DOAJ |
| description | We examined bladder function following spinal cord injury (SCI) by repeated urodynamic investigation (UDI), including external urethral sphincter (EUS) electromyography (EMG) in awake restrained mice and correlated micturition parameters to gene expression and morphological changes in the bladder. A partial bladder outlet obstruction (pBOO) model was used for comparison to elucidate both the common and specific features of obstructive and neurogenic lower urinary tract dysfunction (LUTD). Thirty female C57Bl/6J mice in each group received an implanted bladder catheter with additional electrodes placed next to the EUS in the SCI group. UDI assessments were performed weekly for 7 weeks (pBOO group) or 8 weeks (SCI group), after which bladders were harvested for histological and transcriptome analysis. SCI mice developed detrusor sphincter dyssynergia (DSD) one week after injury with high-pressure oscillations and a significantly increased maximal bladder pressure P<sub>max</sub> and were unable to void spontaneously during the whole observation period. They showed an increased bladder-to-bodyweight ratio, bladder fibrosis, and transcriptome changes indicative of extracellular matrix remodeling and alterations of neuronal signaling and muscle contraction. In contrast, pBOO led to a significantly increased P<sub>max</sub> after one week, which normalized at later time points. Increased bladder-to-bodyweight ratio and pronounced gene expression changes involving immune and inflammatory pathways were observed 7 weeks after pBOO. Comparative transcriptome analysis of SCI and pBOO bladders revealed the activation of Wnt and TGF-beta signaling in both the neurogenic and obstructive LUTD and highlighted FGF2 as a major upregulated transcription factor during organ remodeling. We conclude that SCI-induced DSD in mice leads to profound changes in neuronal signaling and muscle contractility, leading to bladder fibrosis. In a similar time frame, significant bladder remodeling following pBOO allowed for functional compensation, preserving normal micturition parameters. |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T09:42:13Z |
| publishDate | 2023-01-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-c5b66bca76474f44b02dc294dea9ca892023-11-16T16:57:26ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-01-01243245110.3390/ijms24032451Molecular Characterization of Non-Neurogenic and Neurogenic Lower Urinary Tract Dysfunction (LUTD) in SCI-Induced and Partial Bladder Outlet Obstruction Mouse ModelsMichelle von Siebenthal0Akshay Akshay1Mustafa Besic2Marc P. Schneider3Ali Hashemi Gheinani4Fiona C. Burkhard5Katia Monastyrskaya6Functional Urology Research Laboratory, Department for BioMedical Research DBMR, University of Bern, 3008 Bern, SwitzerlandFunctional Urology Research Laboratory, Department for BioMedical Research DBMR, University of Bern, 3008 Bern, SwitzerlandFunctional Urology Research Laboratory, Department for BioMedical Research DBMR, University of Bern, 3008 Bern, SwitzerlandFunctional Urology Research Laboratory, Department for BioMedical Research DBMR, University of Bern, 3008 Bern, SwitzerlandFunctional Urology Research Laboratory, Department for BioMedical Research DBMR, University of Bern, 3008 Bern, SwitzerlandFunctional Urology Research Laboratory, Department for BioMedical Research DBMR, University of Bern, 3008 Bern, SwitzerlandFunctional Urology Research Laboratory, Department for BioMedical Research DBMR, University of Bern, 3008 Bern, SwitzerlandWe examined bladder function following spinal cord injury (SCI) by repeated urodynamic investigation (UDI), including external urethral sphincter (EUS) electromyography (EMG) in awake restrained mice and correlated micturition parameters to gene expression and morphological changes in the bladder. A partial bladder outlet obstruction (pBOO) model was used for comparison to elucidate both the common and specific features of obstructive and neurogenic lower urinary tract dysfunction (LUTD). Thirty female C57Bl/6J mice in each group received an implanted bladder catheter with additional electrodes placed next to the EUS in the SCI group. UDI assessments were performed weekly for 7 weeks (pBOO group) or 8 weeks (SCI group), after which bladders were harvested for histological and transcriptome analysis. SCI mice developed detrusor sphincter dyssynergia (DSD) one week after injury with high-pressure oscillations and a significantly increased maximal bladder pressure P<sub>max</sub> and were unable to void spontaneously during the whole observation period. They showed an increased bladder-to-bodyweight ratio, bladder fibrosis, and transcriptome changes indicative of extracellular matrix remodeling and alterations of neuronal signaling and muscle contraction. In contrast, pBOO led to a significantly increased P<sub>max</sub> after one week, which normalized at later time points. Increased bladder-to-bodyweight ratio and pronounced gene expression changes involving immune and inflammatory pathways were observed 7 weeks after pBOO. Comparative transcriptome analysis of SCI and pBOO bladders revealed the activation of Wnt and TGF-beta signaling in both the neurogenic and obstructive LUTD and highlighted FGF2 as a major upregulated transcription factor during organ remodeling. We conclude that SCI-induced DSD in mice leads to profound changes in neuronal signaling and muscle contractility, leading to bladder fibrosis. In a similar time frame, significant bladder remodeling following pBOO allowed for functional compensation, preserving normal micturition parameters.https://www.mdpi.com/1422-0067/24/3/2451bladder remodelingurodynamic investigation (UDI)external urethral sphincter (EUS)electromyography (EMG)transcriptomedyssynergia |
| spellingShingle | Michelle von Siebenthal Akshay Akshay Mustafa Besic Marc P. Schneider Ali Hashemi Gheinani Fiona C. Burkhard Katia Monastyrskaya Molecular Characterization of Non-Neurogenic and Neurogenic Lower Urinary Tract Dysfunction (LUTD) in SCI-Induced and Partial Bladder Outlet Obstruction Mouse Models International Journal of Molecular Sciences bladder remodeling urodynamic investigation (UDI) external urethral sphincter (EUS) electromyography (EMG) transcriptome dyssynergia |
| title | Molecular Characterization of Non-Neurogenic and Neurogenic Lower Urinary Tract Dysfunction (LUTD) in SCI-Induced and Partial Bladder Outlet Obstruction Mouse Models |
| title_full | Molecular Characterization of Non-Neurogenic and Neurogenic Lower Urinary Tract Dysfunction (LUTD) in SCI-Induced and Partial Bladder Outlet Obstruction Mouse Models |
| title_fullStr | Molecular Characterization of Non-Neurogenic and Neurogenic Lower Urinary Tract Dysfunction (LUTD) in SCI-Induced and Partial Bladder Outlet Obstruction Mouse Models |
| title_full_unstemmed | Molecular Characterization of Non-Neurogenic and Neurogenic Lower Urinary Tract Dysfunction (LUTD) in SCI-Induced and Partial Bladder Outlet Obstruction Mouse Models |
| title_short | Molecular Characterization of Non-Neurogenic and Neurogenic Lower Urinary Tract Dysfunction (LUTD) in SCI-Induced and Partial Bladder Outlet Obstruction Mouse Models |
| title_sort | molecular characterization of non neurogenic and neurogenic lower urinary tract dysfunction lutd in sci induced and partial bladder outlet obstruction mouse models |
| topic | bladder remodeling urodynamic investigation (UDI) external urethral sphincter (EUS) electromyography (EMG) transcriptome dyssynergia |
| url | https://www.mdpi.com/1422-0067/24/3/2451 |
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