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Mechanism of Social Stress-Related Erectile Dysfunction in Mice: Impaired Parasympathetic Neurotransmission and
Shu-Yu Wu1,2, Tze-Chen Chao1, Chun-Kai Hsu1,2
1Department of Urology, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei 23142, Taiwan.
Abstract:
This study aimed to investigate the mechanism underlying social stress (SS)-induced erectile dysfunction (ED) and evaluate the effects of a single subanesthetic dose of ketamine on SS-related ED. Male FVB mice were exposed to retired male C57BL/6 mice for 60 min daily over a 4-week period. In the third week, these FVB mice received intraperitoneal injections of either saline (SSS group) or ketamine (SSK group). Erectile function was assessed by measuring the intracavernosal pressure (ICP) during electrical stimulation of the major pelvic ganglia. Corpus cavernosum (CC) strips were utilized for wire myography to assess their reactivity. Both SSS and SSK mice exhibited significantly lower ICP in response to electrical stimulation than control mice. SS mice showed increased contractility of the CC induced by phenylephrine. Acetylcholine-induced relaxation was significantly reduced in SSS and SSK mice. Sodium nitroprusside-induced relaxation was higher in SSS mice compared to control and SSK mice. Nicotine-induced neurogenic and nitric oxide-dependent relaxation was significantly impaired in both SSS and SSK mice. An immunohistochemical analysis revealed co-localization of tyrosine hydroxylase and neuronal nitric oxide synthase-immunoreactive fibers in the CC. These findings highlight the complex nature of SS-related ED and suggest the limited efficacy of ketamine as a therapeutic intervention.
Insights
Social stress causes erectile dysfunction (ED) by altering corpus cavernosum (CC) function. Ketamine showed limited efficacy in treating this stress-induced ED in mice.
Area of Science:
- Neuroscience
- Urology
- Pharmacology
Background:
- Social stress (SS) is a known contributor to erectile dysfunction (ED).
- The underlying mechanisms of SS-induced ED and potential therapeutic interventions require further investigation.
Purpose of the Study:
- To elucidate the mechanism of social stress-induced erectile dysfunction.
- To evaluate the therapeutic potential of a single subanesthetic ketamine dose on SS-related ED.
Main Methods:
- Male FVB mice were subjected to social stress for 4 weeks.
- Experimental groups received either saline or ketamine injections.
- Erectile function was assessed via intracavernosal pressure (ICP) measurements and ex vivo corpus cavernosum (CC) strip myography.
Main Results:
- Both saline-treated and ketamine-treated stressed mice exhibited significantly reduced ICP.
- SS-induced ED involved increased CC contractility and impaired acetylcholine- and nicotine-induced relaxation.
- Ketamine demonstrated limited efficacy in reversing SS-induced functional deficits in erectile tissue.
Conclusions:
- Social stress significantly impairs erectile function through complex alterations in CC physiology.
- A single subanesthetic ketamine dose has limited therapeutic benefit for social stress-induced erectile dysfunction.
- Further research is needed to understand the neurobiological pathways involved in SS-related ED.
