title: Temporal changes in neurotrophic factors and neurite outgrowth in the major pelvic ganglion following cavernous nerve injury.
abstract: Despite nerve-sparing radical prostatectomy, nerve damage and erectile dysfunction (ED) prevail, and preventing neurodegeneration is of great importance. Neurotrophic factors and neurite outgrowth were characterized in major pelvic ganglia (MPG) following bilateral cavernous nerve injury (BCNI). Young male Sprague-Dawley rats underwent sham or BCNI surgery, and the intracavernosal pressure to mean arterial pressure ratio was measured 2, 7, 14, 21, 30, and 60 days following injury (n = 8/group). MPG gene expression (qPCR) and Western blot were performed for glial cell line-derived neurotrophic factor (GDNF), nerve growth factor (NGF), neurturin, neurotrophin (NT)-3, NT4, brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor, and activating transcription factor 3 (ATF3). Additional rats were injured, and MPGs were removed 24 hr, 48 hr, 3 days, and 7 days following BCNI (n = 3/group). MPGs were cultured in Matrigel, and neurite outgrowth was measured. Erections were impaired early and improved by 60 days in BCNI rats. GDNF, NGF, BDNF, and ATF3 gene expression was significantly increased and NT3 was decreased in MPGs following BCNI (48 hr to 21 days, P < 0.05). GDNF and NGF protein levels were elevated in 48-hr BCNI rats. MPG neurite outgrowth from 24-hr and 48-hr BCNI was higher than sham (658 ± 19 μm, 607 ± 24 μm, 393 ± 23 μm, respectively, P < 0.05). Further studies examining the roles of neurotrophic factors in modulating signaling pathways may provide therapeutic avenues for neurogenically mediated ED.
authors: The James Buchanan Brady Urological Institute and Department of Urology, Johns Hopkins School of Medicine, Baltimore, Maryland.
authors: Johanna L
authors: JL
authors: Hannan
authors: Maarten
authors: M
authors: Albersen
authors: Bernard L
authors: BL
authors: Stopak
authors: Xiaopu
authors: X
authors: Liu
authors: Arthur L
authors: AL
authors: Burnett
authors: Ahmet
authors: A
authors: Hoke
authors: Trinity J
authors: TJ
authors: Bivalacqua
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D018929:Cell Culture Techniques; D004195:Disease Models, Animal; D007172:Erectile Dysfunction / Q000209:etiology; D005728:Ganglia, Sympathetic / Q000378:metabolism* / Q000473:pathology*; D005786:Gene Expression Regulation / Q000502:physiology; D007041:Hypoxanthine Phosphoribosyltransferase / Q000378:metabolism; D008297:Male; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism*; D016501:Neurites / Q000502:physiology*; D059348:Peripheral Nerve Injuries / Q000150:complications / Q000473:pathology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013223:Statistics as Topic
chemical_list: D009414:Nerve Growth Factors; D012333:RNA, Messenger; D007041:Hypoxanthine Phosphoribosyltransferase
keywords: activating transcription factor 3; erectile dysfunction; neurite outgrowth; peripheral nerve injury
references: Brain Res. 1992 Aug 14;588(1):29-40
references: 1382805
references: Cell Tissue Res. 2000 Dec;302(3):321-9
references: 11151444
references: J Sex Med. 2013 Mar;10(3):730-7
references: 23237228
references: J Mol Neurosci. 2010 Nov;42(3):370-7
references: 20407844
references: Cells Tissues Organs. 2001;169(4):410-21
references: 11490121
references: Eur Urol. 2012 Apr;61(4):664-75
references: 22169079
references: BJU Int. 2012 May;109(10):1552-64
references: 22300381
references: Gene Ther. 2007 Sep;14(18):1344-52
references: 17611585
references: Nature. 1996 Jul 4;382(6586):80-3
references: 8657309
references: J Neurosci. 1998 Jan 1;18(1):328-38
references: 9412511
references: J Sex Med. 2006 Sep;3(5):821-7; discussion 828-9
references: 16942527
references: Gene Ther. 2009 Jan;16(1):26-33
references: 18668142
references: J Neurosci. 2007 Jul 25;27(30):7911-20
references: 17652582
references: J Urol. 1991 Aug;146(2):463-8
references: 1856953
references: J Urol. 2013 Mar;189(3):1155-61
references: 23021998
references: Nat Rev Neurol. 2013 Dec;9(12):668-76
references: 24217518
references: Eur Urol. 2007 Aug;52(2):574-80
references: 17097800
references: J Urol. 2001 Jun;165(6 Pt 1):2103-9
references: 11371936
references: J Sex Med. 2006 Sep;3(5):815-20
references: 16942526
references: Mol Cell Neurosci. 2000 Feb;15(2):170-82
references: 10673325
references: Nat Rev Neurosci. 2005 Aug;6(8):615-25
references: 16062170
references: BJU Int. 2003 Sep;92(4):470-5
references: 12930443
references: BJU Int. 2010 Jan;105(1):114-20
references: 19493269
references: BJU Int. 2003 Oct;92(6):631-5
references: 14511050
references: J Sex Med. 2010 Oct;7(10):3351-64
references: 20646178
references: Front Mol Neurosci. 2011 Dec 12;4:53
references: 22180737
references: J Brachial Plex Peripher Nerve Inj. 2007 Mar 06;2:5
references: 17341313
references: Eur J Neurosci. 2006 Nov;24(10):2721-30
references: 17156198
references: Trends Neurosci. 1997 May;20(5):227-31
references: 9141200
references: JAMA. 2014 Apr 2;311(13):1300-7
references: 24691606
references: J Sex Med. 2014 Jun;11(6):1442-51
references: 24636283
references: Eur Urol. 2014 Mar;65(3):587-96
references: 24169081
references: J Sex Med. 2014 Jul;11(7):1685-93
references: 24831646
references: Neurosci Lett. 1999 Nov 5;275(1):45-8
references: 10554981
references: BMC Neurosci. 2006;7:41
references: 16716234
references: Neurosci Lett. 1994 May 23;173(1-2):94-8
references: 7936432
references: Neuroreport. 2000 Jun 5;11(8):1651-4
references: 10852218