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In vitro high glucose increases apoptosis, decreases nerve outgrowth, and promotes survival of sympathetic pelvic neurons.
- Source :
-
Sexual medicine [Sex Med] 2023 Feb 01; Vol. 11 (1), pp. qfac009. Date of Electronic Publication: 2023 Feb 01 (Print Publication: 2023). - Publication Year :
- 2023
-
Abstract
- Background: Diabetes mellitus (DM) is a common cause of erectile dysfunction (ED), yet the molecular basis of DM neurogenic ED remains unknown.<br />Aim: In this study we examined the impact of high glucose on survival and growth of primary cultured pelvic neurons in a rat model and assessed whether coculturing with healthy Schwann cells (SCs) can rescue pelvic neuron growth in patients with DM.<br />Methods: Major pelvic ganglia (MPGs) from adult male Sprague Dawley rats ( n = 8) were dissociated and plated on coverslips. Neurons were exposed to high glucose (45 mM) for 24 or 48 hours and compared to time-matched controls (25 mM). Neurons were stained for neuron-specific beta-tubulin, neuronal nitric oxide synthase, vesicular acetylcholine transferase, tyrosine hydroxylase, and TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling) assay. Schwann cells were dissociated from MPGs of healthy male Sprague Dawley rats ( n = 4) and grown to confluence. Additional Sprague Dawley rats were made diabetic with streptozotocin (50 mg/kg, n = 4), and 5 weeks later MPGs were collected from these rats, dissociated, and cocultured on healthy SCs. Neurons and SCs were stained with beta-tubulin and S100.<br />Outcomes: Length, branching, and survival of nitrergic, parasympathetic, and sympathetic neurons was assessed in neurons exposed to normal or high glucose concentrations, and neuron length was measured in neuron-SC coculture.<br />Results: The total number of neurons and the length and number of branches were significantly decreased after 24 and 48 hours of high glucose ( P < .05). The percentage of nitrergic neurons decreased 10% after 24 hours and 50% after 48 hours of high glucose ( P < .05). After 24 hours of high glucose, cholinergic-positive neurons were unchanged; however, these neurons decreased 30% after 48 hours ( P < .05). The proportion of sympathetic neurons increased 25% after 48 hours of high glucose ( P < .05). At both timepoints, there was a 2-fold increase in the total apoptotic neurons with high glucose ( P < .05). Neurite outgrowth recovered to control lengths after coculture of diabetic neurons with healthy SCs ( P < .05).<br />Clinical Translation: Glucose can be used as a tool to investigate the direct effects of DM on neuritogenesis. Our data suggest that an effective treatment for DM ED protects and repairs the penile neuronal supply.<br />Strengths and Limitations: Exposing MPG neurons to high glucose offers a quick and, inexpensive proxy for DM-related conditions. A limitation of our study is that our model reflects type 1 DM, whereas clinically, most diabetic ED patients have type 2 DM.<br />Conclusion: Culturing pelvic neurons in high glucose can be used as a tool to elucidate how to protect proerectile neurons from cell death and may lead to new therapeutic strategies for diabetic men suffering from ED.<br /> (© The Author(s) 2023. Published by Oxford University Press on behalf of The International Society of Sexual Medicine.)
Details
- Language :
- English
- ISSN :
- 2050-1161
- Volume :
- 11
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Sexual medicine
- Publication Type :
- Academic Journal
- Accession number :
- 37007853
- Full Text :
- https://doi.org/10.1093/sexmed/qfac009