Streptozotocin-induced diabetes causes upregulation of serotonin (5-HT)2A/C receptors in lumbosacral cord motoneurons and down regulation of serotonergic paraneurons in the urethra

Brain Res. 2019 Jul 15:1715:21-26. doi: 10.1016/j.brainres.2019.03.009. Epub 2019 Mar 14.

Abstract

Lower urinary tract (LUT) dysfunction is the most common complication of diabetes mellitus (DM). An involvement of the 5-HT2A receptor in spinal micturition control has been demonstrated in urethane anaesthetized DM rats in which i.v. administration of the 5-HT2A/2C receptor agonist 2,5-methoxy-4-iodoamphetamine (DOI), stimulated high frequency oscillations (HFOs) and improved micturition. However, the mechanisms involved in these effects are not completely understood. The present work showed that 5-HT2A and -2C receptors were upregulated in lumbosacral cord motoneurons, and the number of serotonergic paraneurons were downregulated in the urethra in DM group. The importance of the downregulation of urethral paraneurons in DM remains to be elucidated but may be related to the reduced urethral sensation caused by the disease. We suggest that targets of 5-HT receptor agonists for improvement of voiding function may be found both in the LUT and lumbosacral spinal cord.

Keywords: 5-HT(2A/2C) receptor; Diabetes mellitus; Lumbosacral cord motoneurons; Paraneurons.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Diabetes Mellitus, Experimental / metabolism
  • Diabetes Mellitus, Experimental / physiopathology*
  • Female
  • Lumbosacral Region / physiopathology
  • Motor Neurons / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Serotonin, 5-HT2A / metabolism
  • Receptor, Serotonin, 5-HT2C / metabolism
  • Receptors, Serotonin, 5-HT2 / genetics
  • Receptors, Serotonin, 5-HT2 / metabolism*
  • Serotonergic Neurons / metabolism
  • Serotonin / metabolism
  • Serotonin 5-HT2 Receptor Antagonists / pharmacology
  • Serotonin Receptor Agonists / pharmacology
  • Spinal Cord / drug effects
  • Streptozocin / pharmacology
  • Transcriptional Activation / drug effects
  • Urethra / physiopathology
  • Urinary Bladder / physiopathology

Substances

  • Receptor, Serotonin, 5-HT2A
  • Receptor, Serotonin, 5-HT2C
  • Receptors, Serotonin, 5-HT2
  • Serotonin 5-HT2 Receptor Antagonists
  • Serotonin Receptor Agonists
  • Serotonin
  • Streptozocin