Sex differences in the manifestation of peripheral diabetic neuropathy in gonadectomized rats: a correlation with the levels of neuroactive steroids in the sciatic nerve.

Abstract

Clinical observations suggest a sex-dimorphism in the incidence and symptomatology of diabetic neuropathy, but this possible gender effect has never been investigated in detail in a well-characterized experimental model such as streptozotocin (STZ)-induced diabetes. Therefore, in this study we have compared with a multimodal set of tests the impact of diabetes on the sciatic nerve in male and female rats. To assess whether sex-dimorphism in peripheral diabetic neuropathy is dependent on gonadal hormones we have also analyzed the effect of ovariectomy and orchidectomy on the sciatic nerve of STZ-diabetic rats. Nerve conduction velocity (NCV), Na(+),K(+)-ATPase activity, expression of myelin proteins, thermal sensitivity and reactive oxygen species production were similarly affected in male and female animals by STZ. However, ovariectomy, but not orchidectomy, significantly counteracted STZ-induced alterations on NCV, Na(+),K(+)-ATPase activity, and expression of myelin proteins. This effect of ovariactomy was associated to an increase in the levels of neuroactive steroids, such as dehydroepiandrosterone, testosterone and dihydrotestosterone, in the sciatic nerve of diabetic rats. These neuroactive steroids have been demonstrated to be protective agents in this experimental model of diabetic neuropathy. However, their efficacy has been so far tested only in male animals. Therefore, the present data might represent an important background to evaluate their efficacy also in female diabetic animals.

• Authors: Marzia Pesaresi, Silvia Giatti, Guido Cavaletti, Federico Abbiati, Donato Calabrese, Roberto Bianchi, Donatella Caruso, Luis Miguel Garcia-Segura, Roberto C Melcangi
• Journal: Experimental neurology (Exp Neurol) Vol. 228 Issue 2 Pg. 215-21 (Apr 2011) ISSN: 1090-2430 [Electronic] United States
• PMID: 21241692 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Inc. All rights reserved.

Chemical References

• Steroids

Topics

• Animals
• Diabetes Mellitus, Experimental (metabolism, physiopathology)
• Diabetic Neuropathies (diagnosis, metabolism, physiopathology)
• Female
• Male
• Nerve Fibers, Myelinated (metabolism, pathology)
• Orchiectomy
• Ovariectomy
• Rats
• Rats, Sprague-Dawley
• Sciatic Nerve (metabolism, pathology, physiopathology)
• Sex Characteristics
• Steroids (metabolism)