Testosterone derivatives are neuroprotective agents in experimental diabetic neuropathy

I. Roglio, R. Bianchi, S. Giatti, G. Cavaletti, D. Caruso, S. Scurati, D. Crippa, L. M. Garcia-Segura, F. Camozzi, G. Lauria, R. C. Melcangi

Research output: Contribution to journalArticlepeer-review

Abstract

In this study we have assessed the effect of testosterone (T), dihydrotestosterone (DHT) and 5αandrostan-3α, 17β-diol (3α-diol) therapies on diabetic neuropathy. Diabetes was induced in adult male rats by the injection of streptozotocin and resulted in decreased T and increased 3α-diol levels in plasma and in decreased levels of pregnenolone and DHT in the sciatic nerve. Moreover, a reduced expression of the enzyme converting Tinto DHT (i.e., the 5α-reductase) also occurs at the level of sciatic nerve, suggesting that the decrease of DHT levels could be due to an impairment of this enzyme. Chronic treatment for 1 month with DHT or 3α-diol increased tail nerve conduction velocity and partially counteracted the increase of thermal threshold induced by diabetes. Treatment with DHT increased tibial Na+,K+-ATPase activity and the expression of myelin protein P0 in the sciatic nerve.DHT, 3α-diol and T reversed the reduction of intra-epidermal nerve fiber density induced by diabetes. These observations indicate that T metabolites can reverse behavioral, neurophysiological, morphological and biochemical alterations induced by peripheral diabetic neuropathy.

Original languageEnglish
Pages (from-to)1158-1168
Number of pages11
JournalCellular and Molecular Life Sciences
Volume64
Issue number9
DOIs
Publication statusPublished - May 2007

Keywords

  • 3α-diol
  • 5α-reductase
  • Androgen receptor
  • Dihydrotestosterone
  • Neuroactive steroids
  • Rat
  • Sciatic nerve
  • Streptozotocin

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Cell Biology

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