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

Marzia Pesaresi, Silvia Giatti, Guido Cavaletti, Federico Abbiati, Donato Calabrese, Roberto Bianchi, Donatella Caruso, Luis Miguel Garcia-Segura, Roberto C. Melcangi

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)215-221
Number of pages7
JournalExperimental Neurology
Volume228
Issue number2
DOIs
Publication statusPublished - Apr 2011

Keywords

  • Dehydroepiandrosterone
  • Diabetes
  • Dihydrotestosterone
  • Liquid chromatography-tandem mass spectrometry
  • Neuroprotection
  • Neurosteroids
  • Peripheral nervous system
  • Streptozotocin
  • Testosterone

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience

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    Pesaresi, M., Giatti, S., Cavaletti, G., Abbiati, F., Calabrese, D., Bianchi, R., Caruso, D., Garcia-Segura, L. M., & Melcangi, R. C. (2011). Sex differences in the manifestation of peripheral diabetic neuropathy in gonadectomized rats: A correlation with the levels of neuroactive steroids in the sciatic nerve. Experimental Neurology, 228(2), 215-221. https://doi.org/10.1016/j.expneurol.2011.01.005