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Impact of prostatic radiation therapy on bladder contractility and innervation
Aims To determine the effect of prostatic radiation therapy (RT) on bladder contractility and morphology, and axon, or neuron profiles within the detrusor and major pelvic ganglia (MPG) in male rats. Methods Male Sprague‐Dawley rats (8 weeks) received a single dose of prostatic RT (0 or 22 Gy). Blad...
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| Published in: | Neurourology and urodynamics 2021-08, Vol.40 (6), p.1470-1478 |
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| container_title | Neurourology and urodynamics |
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| creator | Turner, Alexander C. Powers, Shelby A. Odom, Michael R. Pak, Elena S. Ashcraft, Kathleen A. Koontz, Bridget F. Hannan, Johanna L. |
| description | Aims
To determine the effect of prostatic radiation therapy (RT) on bladder contractility and morphology, and axon, or neuron profiles within the detrusor and major pelvic ganglia (MPG) in male rats.
Methods
Male Sprague‐Dawley rats (8 weeks) received a single dose of prostatic RT (0 or 22 Gy). Bladders and MPG were collected 2‐ and 10‐weeks post‐RT. Detrusor contractile responses to carbachol and electrical field stimulation (EFS) were measured. Bladders were stained with Masson's trichrome, and antibodies for nonspecific neuronal marker, cholinergic nerve marker choline acetyltransferase (ChAT), and alpha‐smooth muscle actin. MPG gene expression was assessed by quantitative polymerase chain reaction for ubiquitin carboxy‐terminal hydrolase L1 (Uchl1) and Chat.
Results
At 2 weeks post‐RT, bladder smooth muscle, detrusor cholinergic axon profiles, and MPG Chat gene expression were increased (p |
| doi_str_mv | 10.1002/nau.24705 |
| format | article |
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To determine the effect of prostatic radiation therapy (RT) on bladder contractility and morphology, and axon, or neuron profiles within the detrusor and major pelvic ganglia (MPG) in male rats.
Methods
Male Sprague‐Dawley rats (8 weeks) received a single dose of prostatic RT (0 or 22 Gy). Bladders and MPG were collected 2‐ and 10‐weeks post‐RT. Detrusor contractile responses to carbachol and electrical field stimulation (EFS) were measured. Bladders were stained with Masson's trichrome, and antibodies for nonspecific neuronal marker, cholinergic nerve marker choline acetyltransferase (ChAT), and alpha‐smooth muscle actin. MPG gene expression was assessed by quantitative polymerase chain reaction for ubiquitin carboxy‐terminal hydrolase L1 (Uchl1) and Chat.
Results
At 2 weeks post‐RT, bladder smooth muscle, detrusor cholinergic axon profiles, and MPG Chat gene expression were increased (p < .05), while carbachol and EFS‐mediated contractions were decreased (p < .05). In contrast, at 10 weeks post‐RT, nerve‐mediated contractions were increased compared with control (p < .05), while bladder smooth muscle, detrusor cholinergic axon profiles, MPG Chat expression, and carbachol contractions had normalized. At both 2‐ and 10‐weeks post‐RT, there was no change in detrusor nonspecific axon profiles and MPG Uchl1 expression.
Conclusion
In a rat model, RT of the prostate and MPG was associated with early changes in MPG Chat gene expression, and bladder cholinergic axon profiles and smooth muscle content which resolved over time. After RT recovery, bladder contractility decreased early and increased by 10 weeks. Long‐term changes to the MPG and increased bladder cholinergic axons may contribute to RT‐induced bladder dysfunction in prostate cancer survivors.</description><identifier>ISSN: 0733-2467</identifier><identifier>EISSN: 1520-6777</identifier><identifier>DOI: 10.1002/nau.24705</identifier><identifier>PMID: 34015163</identifier><language>eng</language><publisher>United States: Wiley Subscription Services, Inc</publisher><subject>Acetyltransferase ; Actin ; Axons ; Bladder ; bladder dysfunction ; Carbachol ; Choline ; Choline O-acetyltransferase ; Cholinergic nerves ; Gene expression ; Hydrolase ; Innervation ; Muscle contraction ; Pelvic ganglia ; Polymerase chain reaction ; Prostate ; Prostate cancer ; prostatic radiation ; Radiation therapy ; Smooth muscle ; Ubiquitin</subject><ispartof>Neurourology and urodynamics, 2021-08, Vol.40 (6), p.1470-1478</ispartof><rights>2021 Wiley Periodicals LLC</rights><rights>2021 Wiley Periodicals LLC.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4435-3b34d5db79378c67f1face5e286c86f0075be27185520c3e524573465066a8d33</citedby><cites>FETCH-LOGICAL-c4435-3b34d5db79378c67f1face5e286c86f0075be27185520c3e524573465066a8d33</cites><orcidid>0000-0002-8469-8105 ; 0000-0002-5038-1097</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fnau.24705$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fnau.24705$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>230,315,786,790,891,27957,27958,50923,51032</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34015163$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Turner, Alexander C.</creatorcontrib><creatorcontrib>Powers, Shelby A.</creatorcontrib><creatorcontrib>Odom, Michael R.</creatorcontrib><creatorcontrib>Pak, Elena S.</creatorcontrib><creatorcontrib>Ashcraft, Kathleen A.</creatorcontrib><creatorcontrib>Koontz, Bridget F.</creatorcontrib><creatorcontrib>Hannan, Johanna L.</creatorcontrib><title>Impact of prostatic radiation therapy on bladder contractility and innervation</title><title>Neurourology and urodynamics</title><addtitle>Neurourol Urodyn</addtitle><description>Aims
To determine the effect of prostatic radiation therapy (RT) on bladder contractility and morphology, and axon, or neuron profiles within the detrusor and major pelvic ganglia (MPG) in male rats.
Methods
Male Sprague‐Dawley rats (8 weeks) received a single dose of prostatic RT (0 or 22 Gy). Bladders and MPG were collected 2‐ and 10‐weeks post‐RT. Detrusor contractile responses to carbachol and electrical field stimulation (EFS) were measured. Bladders were stained with Masson's trichrome, and antibodies for nonspecific neuronal marker, cholinergic nerve marker choline acetyltransferase (ChAT), and alpha‐smooth muscle actin. MPG gene expression was assessed by quantitative polymerase chain reaction for ubiquitin carboxy‐terminal hydrolase L1 (Uchl1) and Chat.
Results
At 2 weeks post‐RT, bladder smooth muscle, detrusor cholinergic axon profiles, and MPG Chat gene expression were increased (p < .05), while carbachol and EFS‐mediated contractions were decreased (p < .05). In contrast, at 10 weeks post‐RT, nerve‐mediated contractions were increased compared with control (p < .05), while bladder smooth muscle, detrusor cholinergic axon profiles, MPG Chat expression, and carbachol contractions had normalized. At both 2‐ and 10‐weeks post‐RT, there was no change in detrusor nonspecific axon profiles and MPG Uchl1 expression.
Conclusion
In a rat model, RT of the prostate and MPG was associated with early changes in MPG Chat gene expression, and bladder cholinergic axon profiles and smooth muscle content which resolved over time. After RT recovery, bladder contractility decreased early and increased by 10 weeks. Long‐term changes to the MPG and increased bladder cholinergic axons may contribute to RT‐induced bladder dysfunction in prostate cancer survivors.</description><subject>Acetyltransferase</subject><subject>Actin</subject><subject>Axons</subject><subject>Bladder</subject><subject>bladder dysfunction</subject><subject>Carbachol</subject><subject>Choline</subject><subject>Choline O-acetyltransferase</subject><subject>Cholinergic nerves</subject><subject>Gene expression</subject><subject>Hydrolase</subject><subject>Innervation</subject><subject>Muscle contraction</subject><subject>Pelvic ganglia</subject><subject>Polymerase chain reaction</subject><subject>Prostate</subject><subject>Prostate cancer</subject><subject>prostatic radiation</subject><subject>Radiation therapy</subject><subject>Smooth muscle</subject><subject>Ubiquitin</subject><issn>0733-2467</issn><issn>1520-6777</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><recordid>eNp1kUtLxDAUhYMoOo4u_ANScKOLOnmn3QiD-AIZN846pGnqZOgkNW2V_nvjzCgqmE0u5LvnnpsDwAmClwhCPHGqv8RUQLYDRohhmHIhxC4YQUFIiikXB-CwbZcQwozQfB8cEAoRQ5yMwOxh1SjdJb5KmuDbTnVWJ0GVNhbeJd3CBNUMSSyLWpWlCYn2rguxxda2GxLlysQ6Z8LbuuEI7FWqbs3x9h6D-e3N8_V9-vh093A9fUw1pYSlpCC0ZGUhciIyzUWFKqUNMzjjOuMVhIIVBguUsbiNJoZhygShnEHOVVYSMgZXG92mL1am1ObTUy2bYFcqDNIrK3-_OLuQL_5NZjjP4pQocL4VCP61N20nV7bVpq6VM75vJWYE4XgEjOjZH3Tp--DiepFiJIc5RyhSFxtKx29sg6m-zSAoP1OSMSW5Timypz_df5NfsURgsgHebW2G_5XkbDrfSH4A7Iab9g</recordid><startdate>202108</startdate><enddate>202108</enddate><creator>Turner, Alexander C.</creator><creator>Powers, Shelby A.</creator><creator>Odom, Michael R.</creator><creator>Pak, Elena S.</creator><creator>Ashcraft, Kathleen A.</creator><creator>Koontz, Bridget F.</creator><creator>Hannan, Johanna L.</creator><general>Wiley Subscription Services, Inc</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>7TK</scope><scope>H94</scope><scope>K9.</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-8469-8105</orcidid><orcidid>https://orcid.org/0000-0002-5038-1097</orcidid></search><sort><creationdate>202108</creationdate><title>Impact of prostatic radiation therapy on bladder contractility and innervation</title><author>Turner, Alexander C. ; Powers, Shelby A. ; Odom, Michael R. ; Pak, Elena S. ; Ashcraft, Kathleen A. ; Koontz, Bridget F. ; Hannan, Johanna L.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4435-3b34d5db79378c67f1face5e286c86f0075be27185520c3e524573465066a8d33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Acetyltransferase</topic><topic>Actin</topic><topic>Axons</topic><topic>Bladder</topic><topic>bladder dysfunction</topic><topic>Carbachol</topic><topic>Choline</topic><topic>Choline O-acetyltransferase</topic><topic>Cholinergic nerves</topic><topic>Gene expression</topic><topic>Hydrolase</topic><topic>Innervation</topic><topic>Muscle contraction</topic><topic>Pelvic ganglia</topic><topic>Polymerase chain reaction</topic><topic>Prostate</topic><topic>Prostate cancer</topic><topic>prostatic radiation</topic><topic>Radiation therapy</topic><topic>Smooth muscle</topic><topic>Ubiquitin</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Turner, Alexander C.</creatorcontrib><creatorcontrib>Powers, Shelby A.</creatorcontrib><creatorcontrib>Odom, Michael R.</creatorcontrib><creatorcontrib>Pak, Elena S.</creatorcontrib><creatorcontrib>Ashcraft, Kathleen A.</creatorcontrib><creatorcontrib>Koontz, Bridget F.</creatorcontrib><creatorcontrib>Hannan, Johanna L.</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Neurourology and urodynamics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Turner, Alexander C.</au><au>Powers, Shelby A.</au><au>Odom, Michael R.</au><au>Pak, Elena S.</au><au>Ashcraft, Kathleen A.</au><au>Koontz, Bridget F.</au><au>Hannan, Johanna L.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Impact of prostatic radiation therapy on bladder contractility and innervation</atitle><jtitle>Neurourology and urodynamics</jtitle><addtitle>Neurourol Urodyn</addtitle><date>2021-08</date><risdate>2021</risdate><volume>40</volume><issue>6</issue><spage>1470</spage><epage>1478</epage><pages>1470-1478</pages><issn>0733-2467</issn><eissn>1520-6777</eissn><notes>ObjectType-Article-1</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-2</notes><notes>content type line 23</notes><notes><![CDATA[Author Contributions (CRediT statement): ACT: Methodology, Validation, Formal analysis, Investigation, Writing- Original draft preparation/Review & Editing; SAP: Conceptualization, Methodology, Validation, Investigation, Writing- Review & Editing; MRO: Methodology, Investigation, Writing- Review & Editing; ESP: Methodology, Validation, Investigation, Supervision, Writing – Review & Editing; KAA: Methodology, Investigation, Writing – Review & Editing; BFK: Conceptualization, Methodology, Resources, Writing – Review & Editing; JLH: Conceptualization, Methodology, Resources, Writing – Review & Editing, Supervision, Product administration, Funding acquisition.]]></notes><abstract>Aims
To determine the effect of prostatic radiation therapy (RT) on bladder contractility and morphology, and axon, or neuron profiles within the detrusor and major pelvic ganglia (MPG) in male rats.
Methods
Male Sprague‐Dawley rats (8 weeks) received a single dose of prostatic RT (0 or 22 Gy). Bladders and MPG were collected 2‐ and 10‐weeks post‐RT. Detrusor contractile responses to carbachol and electrical field stimulation (EFS) were measured. Bladders were stained with Masson's trichrome, and antibodies for nonspecific neuronal marker, cholinergic nerve marker choline acetyltransferase (ChAT), and alpha‐smooth muscle actin. MPG gene expression was assessed by quantitative polymerase chain reaction for ubiquitin carboxy‐terminal hydrolase L1 (Uchl1) and Chat.
Results
At 2 weeks post‐RT, bladder smooth muscle, detrusor cholinergic axon profiles, and MPG Chat gene expression were increased (p < .05), while carbachol and EFS‐mediated contractions were decreased (p < .05). In contrast, at 10 weeks post‐RT, nerve‐mediated contractions were increased compared with control (p < .05), while bladder smooth muscle, detrusor cholinergic axon profiles, MPG Chat expression, and carbachol contractions had normalized. At both 2‐ and 10‐weeks post‐RT, there was no change in detrusor nonspecific axon profiles and MPG Uchl1 expression.
Conclusion
In a rat model, RT of the prostate and MPG was associated with early changes in MPG Chat gene expression, and bladder cholinergic axon profiles and smooth muscle content which resolved over time. After RT recovery, bladder contractility decreased early and increased by 10 weeks. Long‐term changes to the MPG and increased bladder cholinergic axons may contribute to RT‐induced bladder dysfunction in prostate cancer survivors.</abstract><cop>United States</cop><pub>Wiley Subscription Services, Inc</pub><pmid>34015163</pmid><doi>10.1002/nau.24705</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0002-8469-8105</orcidid><orcidid>https://orcid.org/0000-0002-5038-1097</orcidid><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 0733-2467 |
| ispartof | Neurourology and urodynamics, 2021-08, Vol.40 (6), p.1470-1478 |
| issn | 0733-2467 1520-6777 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8298286 |
| source | Wiley-Blackwell Journals |
| subjects | Acetyltransferase Actin Axons Bladder bladder dysfunction Carbachol Choline Choline O-acetyltransferase Cholinergic nerves Gene expression Hydrolase Innervation Muscle contraction Pelvic ganglia Polymerase chain reaction Prostate Prostate cancer prostatic radiation Radiation therapy Smooth muscle Ubiquitin |
| title | Impact of prostatic radiation therapy on bladder contractility and innervation |
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