title: Early-stage Type 2 Diabetes Mellitus Impairs Erectile Function and Neurite Outgrowth From the Major Pelvic Ganglion and Downregulates the Gene Expression of Neurotrophic Factors.
abstract: OBJECTIVE
  To assess neurite sprouting and gene expression of neurotrophic factors, nerve markers, and apoptosis in the major pelvic ganglia (MPGs) of rats with type 2 diabetes mellitus (T2DM) as it relates to erectile function.
  
  
  METHODS
  Male rats were fed high-fat diet for 2 weeks followed by 2 low-dose injections of streptozotocin (20 mg/kg). In 3 groups (controls, 3-week, or 5-week T2DM), erectile function was measured by ratios of intracavernosal pressure to mean arterial pressure after cavernous nerve stimulation. MPGs were harvested, and gene expressions of neurotrophic factor 3, nerve growth factor, glial cell line-derived neurotrophic factor, brain-derived neurotrophic factor, caspase-1, -3, -9, beta tubulin type III, and neuronal nitric oxide synthase were quantified by quantitative polymerase chain reaction. Additional MPGs were harvested and cultured in Matrigel. Neurite outgrowth from the MPG was evaluated at 48 hours after culture.
  
  
  RESULTS
  Erectile function was significantly decreased in all rats with T2DM. Gene expressions of neurotrophic factor 3, nerve growth factor, glial cell line-derived neurotrophic factor, and brain-derived neurotrophic factor were slightly lower at 3 weeks and significantly lower at 5 weeks after T2DM induction. Gene expression of apoptotic markers caspase-1, -3, -9, and neuronal markers beta tubulin type III and neuronal nitric oxide synthase remained unchanged. Rats with T2DM had shorter neurite length and less neurite sprouting than did the control MPG.
  
  
  CONCLUSIONS
  Early-stage T2DM downregulates neurotrophic factors, induces erectile dysfunction, and impairs MPG neurite outgrowth, suggesting that erectile dysfunction may be prevented by supplementing neurotrophic factors at early-stage T2DM.
authors.affiliation: The James Buchanan Brady Urological Institute and Department of Urology, The Johns Hopkins School of Medicine, Baltimore, MD.
authors.forename: Hotaka
authors.initials: H
authors.lastname: Matsui
authors.affiliation: The James Buchanan Brady Urological Institute and Department of Urology, The Johns Hopkins School of Medicine, Baltimore, MD.
authors.forename: Biljana
authors.initials: B
authors.lastname: Musicki
authors.affiliation: The James Buchanan Brady Urological Institute and Department of Urology, The Johns Hopkins School of Medicine, Baltimore, MD.
authors.forename: Nikolai A
authors.initials: NA
authors.lastname: Sopko
authors.affiliation: The James Buchanan Brady Urological Institute and Department of Urology, The Johns Hopkins School of Medicine, Baltimore, MD.
authors.forename: Xiaopu
authors.initials: X
authors.lastname: Liu
authors.affiliation: The James Buchanan Brady Urological Institute and Department of Urology, The Johns Hopkins School of Medicine, Baltimore, MD.
authors.forename: Paula J
authors.initials: PJ
authors.lastname: Hurley
authors.affiliation: The James Buchanan Brady Urological Institute and Department of Urology, The Johns Hopkins School of Medicine, Baltimore, MD.
authors.forename: Arthur L
authors.initials: AL
authors.lastname: Burnett
authors.affiliation: The James Buchanan Brady Urological Institute and Department of Urology, The Johns Hopkins School of Medicine, Baltimore, MD.
authors.forename: Trinity J
authors.initials: TJ
authors.lastname: Bivalacqua
authors.affiliation: Department of Physiology, Brody School of Medicine, East Carolina University, Greenville, NC. Electronic address: hannanj14@ecu.edu.
authors.forename: Johanna L
authors.initials: JL
authors.lastname: Hannan
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000235:genetics* / Q000473:pathology; D015536:Down-Regulation; D007172:Erectile Dysfunction / Q000209:etiology / Q000235:genetics* / Q000503:physiopathology; D005786:Gene Expression Regulation; D007001:Hypogastric Plexus / Q000473:pathology*; D008297:Male; D009414:Nerve Growth Factors / Q000096:biosynthesis / Q000235:genetics*; D010410:Penile Erection / Q000502:physiology; D010413:Penis / Q000294:innervation*; D012313:RNA; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D009414:Nerve Growth Factors; D012313:RNA